Infections Cause Psoriasis

Streptococcal bacteria interact with HLA-Cw*0602 in psoriasis

The role of streptococcal infection in the initiation of guttate psoriasis. NR Telfer, RJ Chalmers, K Whale, G Colman. Arch Dermatol 1992 Jan;128(1):39-42. 111 patients with a sudden onset or deterioration of psoriasis. "Serologic evidence of recent streptococcal infection was present in 19 (58%) of 33 patients with acute guttate psoriasis compared with seven (26%) of 27 patients with guttate exacerbations of chronic psoriasis. Streptococcus pyogenes was isolated from 19 (17%) of all 111 patients (9 [26%] of 34 with acute guttate psoriasis, four [13%] of 30 with guttate exacerbations of chronic psoriasis, and five [14%] of 37 patients with chronic psoriasis) compared with seven (7%) of 101 of a control population of patients being seen for treatment of viral warts. Other beta-hemolytic streptococci were found with equal frequency in the study and control populations. Thirteen isolates of 10 different streptococcal serotypes were obtained from the 64 patients with guttate psoriasis. These serotypes were similar in distribution and prevalence to those present in the local community."

Telfer - Arch Dermatol 1992 abstract / PubMed

Epidermal HLA-DR and the enhancement of cutaneous reactivity to superantigenic toxins in psoriasis. JB Travers, QA Hamid, DA Norris, C Kuhn, RC Giorno, PM Schlievert, ER Farmer, DY Leung. J Clin Invest 1999 Nov;104(9):1181-1189. Toxic shock syndrome toxin-1 (TSST-1), staphylococcal enterotoxin type B, and streptococcal pyogenic enterotoxin types A and C triggered a significantly greater inflammatory skin response in psoriatics than in normal control subjects or in subjects with atopic dermatitis or lichen planus. "Immunohistochemical studies revealed significantly higher HLA-DR expression in keratinocytes from psoriatics than from controls. However, a mutant TSST-1 protein that fails to bind HLA-DR did not elicit an inflammatory skin reaction. These results indicate that keratinocyte expression of HLA-DR enhances inflammatory skin responses to SAg's."

Travers - J Clin Invest 1999 abstract / PubMed

Subclinical microbial infection in patients with chronic plaque psoriasis. I Bartenjev, M Rogl Butina, M Potocnik. Acta Derm Venereol Suppl (Stockh) 2000;(211):17-18. 195 patients with severe chronic plaque psoriasis hospitalized between 1996 and 1998. "Subclinical streptococcal and/or staphylococcal infections were detected in 68% of tested patients and in only 11% of the control group."

Bartenjev - Acta Derm Venereol Suppl (Stockh) 2000 abstract / PubMed

HLA-C and guttate psoriasis. E Mallon, M Bunce, H Savoie, A Rowe, R Newson, F Gotch, CB Bunker. Br J Dermatol 2000 Dec;143(6):1177-1182. 29 caucasian patients with guttate psoriasis presenting consecutively with guttate psoriasis associated with a history of a sore throat and/or an antistreptolysin O titre > 200 IU mL-1, versus a 604 random caucasian cadaver controls. "All patients (100%) with guttate psoriasis carried the Cw*0602 allele compared with 20% of the control population (odds ratio = infinity; 95% confidence limits 25.00-infinity; Pcorrected < 0.0000002)."

Mallon - Br J Dermatol 2000 abstract / PubMed

Contrasting patterns of streptococcal superantigen-induced T-cell proliferation in guttate vs. chronic plaque psoriasis. SC Davison, MH Allen, E Mallon, JN Barker. Br J Dermatol 2001 Aug;145(2):245-251. "Peripheral blood mononuclear cells from patients with active GP showed a twofold increased proliferation after stimulation with streptococcal pyogenic toxins A and streptococcal pyogenic toxins C compared with controls (P < 0.01), whereas the response to the staphylococcal toxins and mitogenic stimulation was the same in all groups. Peripheral blood lymphocytes (PBL) from patients with active GP showed increased use of the superantigen-reactive families Vbeta2 (P < 0.01) and Vbeta17 (P < 0.05), which was not evident in the other patient groups or controls. This pattern of Vbeta expression was only observed in CLA-positive T cells. Furthermore, there was a positive correlation between Vbeta2 expression and enhanced proliferation after stimulation with SPEA (r = 0.82, P < 0.01) and SPEC (r = 0.74, P < 0.05) in active GP."

Davison - Br J Dermatol 2001 abstract / PubMed

Epidermal CD8+ T cells reactive with group A streptococcal antigens in chronic plaque psoriasis. JM Ovigne, BS Baker, SC Davison, AV Powles, L Fry. Exp Dermatol 2002 Aug;11(4):357-364. "A subset of GAS-reactive CD8+ T cells (2.4% +/- 2.4) was found in 14/21 (67%) fresh cell suspensions. A smaller subset of GAS-reactive CD4+ T cells (0.9% +/- 0.9) was found in 13/21 (62%) fresh cell suspensions, which was expanded in the T cell lines. There was a significant inverse correlation between the proportions of GAS-reactive CD4+ and CD8+ T cells in the fresh suspensions (r = -0.48, P = 0.0277). The presence of GAS-reactive CD4+ or CD8+ T cells did not correlate with HLA-DR7 or HLA-Cw6 expression, respectively."

Ovigne - Exp Dermatol 2002 abstract / PubMed

Increased microorganisms DNA levels in peripheral blood monocytes from psoriatic patients using PCR with universal ribosomal RNA primers. Y Okubo, N Oki, H Takeda, M Amaya, S Ito, M Osada, M Utsumi, M Koga, H Kawashima. J Dermatol 2002 Sep;29(9):547-555. 15 patients with psoriasis vulgaris and 2 healthy controls. "[B]acterial 16S DNA levels in monocytes were significantly higher in psoriatic patients than in controls. The fungal 18S DNA levels were also higher in psoriatic patients than in controls, but the differences were not significant. Although the microorganisms DNA levels in monocytes of psoriatic patients were high, there was no correlation between the bacterial DNA levels in monocytes of the psoriatics and PASI scores. Our study suggests that monocytes in psoriatic patients engulf more bacteria than there in controls, causing an activation of monocytes and triggering the formation of new lesions in the initial stages of psoriasis."

Okubo - J Dermatol 2002 abstract / PubMed

Streptococcal infection distinguishes different types of psoriasis. P Weisenseel, B Laumbacher, P Besgen, D Ludolph-Hauser, T Herzinger, M Roecken, R Wank, JC Prinz. J Med Genet 2002 Oct;39(10):767-768. 96 white patients with non-pustular chronic plaque psoriasis, 367 healthy controls. "HLA typing showed a significantly increased frequency of HLA-Cw6, -B57, and -B13 in psoriasis patients compared to 367 healthy controls (p<0.001 each), confirming earlier findings. Evidence of group A streptococcal infection was found exclusively in type I psoriasis patients (table 1). The difference compared to type II patients was significant (p=0.004)." Type I psoriasis begins before age 40 and there is often a family history.

Weisenseel / J Med Genet 2002 full article

Streptococcal throat infections and exacerbation of chronic plaque psoriasis: a prospective study. JE Gudjonsson, AM Thorarinsson, B Sigurgeirsson, KG Kristinsson, H Valdimarsson. Br J Dermatol 2003 Sep;149(3):530-534. 208 patients with chronic plaque psoriasis and 116 controls. "The psoriasis patients reported sore throat significantly more often than controls (61 of 208 vs. three of 116, P < 0.0001), and beta-haemolytic streptococci of Lancefield groups A, C and G (M protein-positive streptococci) were more often cultured from the patients than the controls (19 of 208 vs. one of 116, P = 0.003). A significant exacerbation of psoriasis (P = 0.004) was observed only if streptococci were isolated and the patients were assessed 4 days or later after the onset of sore throat. No difference was observed between groups A, C or G streptococci in this respect."

Gudjonsson - Br J Dermatol 2003 abstract / PubMed

IgG class antibodies from psoriasis patients recognize the 60-KDa heat-shock protein of Streptococcus pyogenes. ME Cancino-Díaz, V Ruiz-González, L Ramírez-Reséndiz, B Ortiz, ML Domínguez-López, GC Paredes-Cabrera, G León-Dorantes, F Blancas-González, L Jiménez-Zamudio, E García-Latorre. Int J Dermatol 2004 May;43(5):341-347. "The PP infected with S. pyogenes had higher titers of the antirHSP60Sp, high ASO, and high PASI. The PP patients did not significantly recognize the HSP60Ec or the HSP60Hu. The GP patients had a higher response to the rHSP60Sp than the healthy controls or ISp patients (P < 0.05) but showed no association with the disease. The response of the ISp patients to the HSP60Sp was similar to the healthy controls. The response to the rHSP70Sp was similar in the PP patients and the healthy controls. CONCLUSION: Results suggest that a high response to the HSP60Sp could be associated with the chronic form of psoriasis."

Cancino-Díaz - Int J Dermatol 2004 abstract / PubMed

Peripheral blood T cell responses to keratin peptides that share sequences with streptococcal M proteins are largely restricted to skin-homing CD8(+) T cells. A Johnston, JE Gudjonsson, H Sigmundsdottir, TJ Love, H Valdimarsson. Clin Exp Immunol 2004 Oct;138(1):83-93. 12 HLA-Cw*0602-positive patients, 11 Cw6+ healthy individuals with a family history of psoriasis, and 11 Cw6– with psoriasis. "HLA-Cw*0602(+) psoriasis patients had significant CD8(+) T cell interferon (IFN)-gamma responses to peptides from the K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. These responses were about 10 times more frequent in the skin-homing cutaneous lymphocyte-associated antigen-expressing (CLA(+)) subset of CD8(+) T cells. CD4(+) T cells showed only borderline responses. CLA(+) CD8(+) T cells from Cw6(+) non-psoriatic individuals responded to some M6 peptides but rarely to K17 peptides. Cw6(-) psoriasis patients showed a response that was intermediate between Cw6(+) patients and controls."

Johnston - Clin Exp Immunol 2004 full article / PubMed Central
Johnston - Clin Exp Immunol 2004 full article

Acute guttate psoriasis patients have positive streptococcus hemolyticus throat cultures and elevated antistreptococcal M6 protein titers. G Zhao, X Feng, A Na, J Yongqiang, Q Cai, J Kong, H Ma. J Dermatol 2005 Feb;32(2):91-96. 68 patients with acute guttate psoriasis. "A high incidence of Streptococcus hemolyticus culture was observed in the guttate psoriatic group compared with the plaque psoriasis and control groups... we found that the titer of antistreptococcal M6 protein was significantly higher in the serum of guttate psoriasis patients than in the control or plaque psoriasis groups (P < 0.01).

Zhao - J Dermatol 2005 abstract / PubMed

HLA allele associations and V-beta T-lymphocyte expansions in patients with psoriasis, harboring toxin-producing Staphylococcus aureus. R Ajib, L Janbazian, E Rahal, GM Matar, S Zaynoun, AG Kibbi, AM Abdelnoor. J Biomed Biotechnol 2005;2005(4):310-315. 22 patients and 22 controls in Lebanon. A relative risk of 4.7 (P < .05) for HLA-Cw6 was found. S aureus was isolated from the throat of 11 patients. "Enterotoxins A and C were detected by agglutination in the culture filtrate of one isolate. The enterotoxin A and/or C genes were detected by PCR in 9 isolates, and transcripts were detected by RT-PCR in 7 of them. None of the isolates from controls harbored enterotoxin genes. Vβ expansions were detected by RT-PCR in all 22 patients. Low or no Vβ expansions were obtained in controls."

Ajib - J Biomed Biotechnol 2005 full article / PubMed Central

Distinct HLA-C/KIR genotype profile associates with guttate psoriasis. SJ Holm, K Sakuraba, L Mallbris, K Wolk, M Ståhle, FO Sánchez. J Invest Dermatol 2005 Oct;125(4):721-730. 396 psoriatic patients and 372 matched controls. "HLA-Cw6 and position 80 genotyping associated strongly to disease, whereas KIR2DS1 associated weakly. Individuals of the U and EI classes were more common among guttate psoriasis patients, which related to HLA-Cw*0602 status. These results suggest that different levels for NK/NKT cell activation thresholds, not only reduction, contribute to immune deregulation in psoriasis. In the guttate phenotype, balanced HLA-C/KIR interactions might be altered by the presence of concomitant streptococcal infections." "Remarkably, HLA-Cw*0602 was found in 73% of guttate patients (OR=22.70, CI [12.44–41.42], p=2.69 10-28)." "Additionally, PsG patients belonging to class B more often reported a concomitant throat infection at disease onset, confirmed as streptococcal by swab tests."

Holm / J Invest Dermatol 2005 full article

Skin basement membrane zone: a depository for circulating microbial antigen evoking psoriasis and autoimmunity. PW Noah, CR Handorf, RB Skinner Jr, TD Mandrell, EW Rosenberg. Skinmed 2006 Mar-Apr;5(2):72-9; quiz 80-1. "[S]kin biopsies of psoriasis patients thought clinically to have either streptococcal carrier state or gastrointestinal candidal colonization. A polyclonal antibody to streptococcal-derived exoenzymes unlikely to share antigenic structures with normal human skin, and an anticandidal antibody, were used with linked streptavidin biotin amplification stain. The predicted microbial product appeared heavily in lesional epidermis, but unexpectedly also as a thin deposit along the skin basement membrane zone (SBMZ) of apparently unaffected skin. Staining was negative for nonpsoriatic subjects."

Noah - Skinmed 2006 abstract / PubMed

Distinct clinical differences between HLA-Cw*0602 positive and negative psoriasis patients--an analysis of 1019 HLA-C- and HLA-B-typed patients. JE Gudjonsson, A Karason, EH Runarsdottir, AA Antonsdottir, VB Hauksson, HH Jónsson, J Gulcher, K Stefansson, H Valdimarsson. J Invest Dermatol 2006 Apr;126(4):740-745. 654 (64.2%) were HLA-Cw*0602 positive but 365 (35.8%) carried other HLA-C alleles. HLA-Cw*0602 positive patients had higher incidence of guttate and the eruptive type of psoriasis (P<0.0001) and more frequent exacerbations with throat infections (P=0.01). "[T]he HLA-Cw*0602 allele is in the great majority of cases (97%) inherited with one of three HLA-B alleles: B*57, B*37, and B*13. These three allele combinations are therefore often referred to as ancestral haplotypes." Nail lesions were more common in Cw*0602 negative patients and correlated strongly with psoriatic arthritis.

Gudjonsson / J Invest Dermatol 2006 full article

HLA Cw*06 is not essential for streptococcal-induced psoriasis. L Fry, AV Powles, S Corcoran, S Rogers, J Ward, DJ Unsworth. Br J Dermatol 2006 May;154(5):850-853. 105 Irish patients, 64 guttate or guttate-flare, 41 chronic plaque. "The incidence of Cw*06 was 86% in the GG and 73% in the CPG, which was not significantly different (P=0.1725) but the incidence in both groups was significantly higher than in an Irish control group (18%) (P<0.0001 vs. GG and P<0.0001 vs. CPG). Evidence for streptococcal infection was higher in the GG (56%) than in the CPG (32%) (P=0.0231). Of those patients with evidence of streptococcal infection, 30 of 36 GG (83%) and nine of 13 CPG (69%) patients possessed the Cw*06 genotype."

Fry - Br J Dermatol 2006 abstract / PubMed

Increased blood levels of IgG reactive with secreted Streptococcus pyogenes proteins in chronic plaque psoriasis. RG El-Rachkidy, JM Hales, PP Freestone, HS Young, CE Griffiths, RD Camp. J Invest Dermatol 2007 Jun;127(6):1337-1342. 57 patients, 40 volunteers. "[B]lood samples from patients with chronic plaque psoriasis contained significantly higher titers of reactive IgG than samples from age- and sex-matched healthy controls (P=0.0009). In contrast, neither a standard assay measuring antistreptolysin O titers nor ELISAs measuring titers of IgG reactive with protein fractions from Staphylococcus aureus and Staphylococcus epidermidis, were able to distinguish between blood samples from the two groups." Blood from the two sets of donors contained similar titers of IgG reactive with protein fractions from the other bacteria tested.

El-Rachkidy / J Invest Dermatol 2007 full article

HLA-Cw*0602 associates with a twofold higher prevalence of positive streptococcal throat swab at the onset of psoriasis: a case control study. L Mallbris, K Wolk, F Sánchez, M Ståhle. BMC Dermatol 2009 May 29;9:5. 439 with plaque psoriasis, 143 with guttate psoriasis, and 454 healthy controls. "Regardless of disease phenotype, the prevalence of positive streptococcal throat swabs in HLA-Cw*0602 positive patients was twice the prevalence among HLA-Cw*0602 negative patients (OR = 5.8 C.I. = 3.57-9.67, p < 0.001), while no difference was observed among Cw*0602 positive versus negative controls. The corresponding odds ratios for the guttate and plaque psoriasis phenotypes were 3.5 (CI = 1.5-8.7, p = 0.01) and 2.3 (CI = 1.0-5.1, p = 0.02) respectively."

Mallbris - BMC Dermatol 2009 full article / PubMed Central

High prevalence of Staphylococcus aureus cultivation and superantigen production in patients with psoriasis. DD Balci, N Duran, B Ozer, R Gunesacar, Y Onlen, JZ Yenin. Eur J Dermatol 2009 May-Jun;19(3):238-242. Fifty consecutive patients with chronic plaque-type psoriasis and 50 sex- and age-matched healthy controls. "There was a statistical difference in cultivation of S. aureus between lesional (64%) and non-lesional skin (14%) in patients with psoriasis (p \= 0.037). S. aureus was cultivated from the nares in 25 (50%) of 50 patients with psoriasis and in 17 (34%) of 50 healthy controls (p > 0.05). In psoriasis patients, 31 (96.8%) out of the 32 strains isolated from the lesional skin and 3 (42.3%) out of the 7 strains isolated from the non-lesional skin were toxigenic (p \= 0.01). Isolated strains from the nares were toxigenic in 96% (24/25) for patients with psoriasis and in 41.2% (7/17) for healthy controls, respectively (p \= 0.006). Patients with cultivation-positive in lesional skin had a significantly higher PASI score than patients who were cultivation-negative in lesional skin (8.28 ± 3.97 vs. 5.89 ± 2.98, p \= 0.031)."

Balci - Eur J Dermatol 2009 abstract / PubMed
Balci / Eur J Dermatol 2009 full article

Clinical comparison of psoriasis in Korean adults and children: correlation with serum anti-streptolysin O titers. SK Kim, HY Kang, YC Kim, ES Lee. Arch Dermatol Res 2010 May;302(4):295-299. 30 adult and 30 childhood psoriasis patients. "Childhood psoriasis had a facial predominance when compared with the adult psoriasis. The childhood psoriasis patients with high ASO titers had guttate psoriasis more frequently than patients with normal ASO titers. In children with plaque-type psoriasis, psoriasis area and severity index score was increased in the high ASO titer group than normal ASO titer group."

Kim - Arch Dermatol Res 2010 abstract / PubMed

Evidence for the presence of bacteria in the blood of psoriasis patients. OH Munz, S Sela, BS Baker, CE Griffiths, AV Powles, L Fry. Arch Dermatol Res 2010 Sep;302(7):495-498. 20 patients with psoriasis (seven guttate, six chronic plaque and seven chronic plaque with associated guttate flare), and 16 control subjects. "Ribosomal bacterial DNA was detected in the blood of all 20 patients with psoriasis, but in none of the controls. Streptococci were detected in six of seven patients with guttate psoriasis, but none had staphylococci. In contrast, staphylococci were identified in 9 of 13 patients with chronic plaque psoriasis, whilst only 2 demonstrated streptococci. In three psoriasis patients, species other than streptococci and staphylococci were identified."

Munz - Arch Dermatol Res 2010 abstract / PubMed

Genetics of psoriasis: evidence for epistatic interaction between skin barrier abnormalities and immune deviation. JG Bergboer, PL Zeeuwen, J Schalkwijk. J Invest Dermatol 2012 Oct;132(10):2320-2331. Review. "The strongest and invariably reproduced susceptibility locus, PSORS1, harbors HLA-C*06, which was already known to be associated with psoriasis in the 1970s... Given its role in antigen presentation, the association with HLA-C*06 strongly points at a role of the adaptive immune system in psoriasis." The estimated population attributable risk is 29%, based on frequency of HLA-C*06 in control population 0.17 and odds ratio of 3.45.

Bergboer / J Invest Dermatol 2012 full article

Genetic Association with ERAP1 in Psoriasis Is Confined to Disease Onset after Puberty and Not Dependent on HLA-C*06. J Lysell, L Padyukov, I Kockum, P Nikamo, M Ståhle. J Invest Dermatol 2013 Feb;133(2):411-417. 954 cases, 1748 controls. "[A]ssociation with ERAP1 was confined to cases with onset between 10 and 20 years (odds ratio 1.59, 95% confidence interval: 1.28-1.98, P=0.00008) and no association was detected in cases with onset below 10 years, reflecting genetic heterogeneity within the childhood psoriasis population. In contrast to earlier findings, association with ERAP1 was neither dependent on nor interacting with HLA-C*06:02." "In the majority of patients (77%) an associated streptococcal infection was confirmed." A relatively high proportion of cases were of the guttate subtype. "[C]ases with late onset of disease (above 40 years) had significantly lower association with HLA-C*06:02 and also lacked association with ERAP1..." and were also more likely to be plaque subtype.

Lysell - J Invest Dermatol 2013 full article / PubMed Central
Lysell / J Invest Dermatol 2013 full article

Streptococcus Induces Circulating CLA(+) Memory T-Cell-Dependent Epidermal Cell Activation in Psoriasis. M Ferran, AB Galván, C Rincón, ER Romeu, M Sacrista, E Barboza, A Giménez-Arnau, A Celada, RM Pujol, LF Santamaria-Babí. J Invest Dermatol 2013 Apr;133(4):999-1007. "In this study, activation of circulating psoriatic cutaneous lymphocyte-associated antigen (CLA)(+) memory T cells cultured together with epidermal cells occurred only when streptococcal throat extracts were added. This triggered the production of Th1, Th17, and Th22 cytokines, as well as epidermal cell mediators (CXCL8, CXCL9, CXCL10, and CXCL11). Streptococcal extracts (SEs) did not induce any activation with either CLA(-) cells or memory T cells cultured together with epidermal cells from healthy subjects. Intradermal injection of activated culture supernatants into mouse skin induced epidermal hyperplasia. SEs also induced activation when we used epidermal cells from nonlesional skin of psoriatic patients with CLA(+) memory T cells. Significant correlations were found between SE induced upregulation of mRNA expression for ifn-γ, il-17, il-22, ip-10, and serum level of antistreptolysin O in psoriatic patients. This study demonstrates the direct involvement of streptococcal infection in pathological mechanisms of psoriasis, such as IL-17 production and epidermal cell activation."

Ferran - J Invest Dermatol 2013 abstract / PubMed

The association of sore throat and psoriasis may be explained by histologically distinctive tonsils and increased expression of skin homing molecules by tonsil T cells. SL Sigurdardottir, RH Thorleifsdottir, H Valdimarsson, A Johnston. Clin Exp Immunol 2013 Oct;174(1):139-151. "Here we confirm that psoriasis tonsils are more frequently infected by β-haemolytic Streptococci, in particular Group C Streptococcus, compared with recurrently infected tonsils from patients without skin disease. Moreover, we show that tonsils from psoriasis patients contained smaller lymphoid follicles that occupied a smaller tissue area, had a lower germinal centre to marginal zone area ratio and contained fewer tingible body macrophages per unit area compared with recurrently infected tonsils from individuals without skin disease. Psoriasis patients' tonsils had a higher frequency of skin-homing (CLA+) CD4+ and CD8+ T cells and this correlated significantly with their frequency of blood CLA+ T cells. The psoriasis patients also had higher frequency of tonsil T cells expressing the IL-23 receptor that was preferentially expressed by the CLA+ T cell population."

Sigurdardottir - Clin Exp Immunol 2013 abstract / PubMed

Community differentiation of the cutaneous microbiota in psoriasis. AV Alekseyenko, GI Perez-Perez, A De Souza, B Strober, Z Gao, M Bihan, K Li, BA Methé, MJ Blaser. Microbiome 2013 Dec 23;1(1):31. "The taxonomic richness and evenness decreased in both lesion and unaffected communities compared to control. These differences are explained by the combined increased abundance of the four major skin-associated genera (Corynebacterium, Propionibacterium, Staphylococcus, and Streptococcus), which present a potentially useful predictor for clinical skin type."

Alekseyenko - Microbiome 2013 abstract / PubMed

The rise of staphylococcal super antigens in psoriatic patients: a case-control study. N Atefi, S Noorbakhsh, S Ghavidel Darestani, A Tabatabaei, M Rezaee. Jundishapur J Microbiol 2014 May;7(5):e9912. 41 psoriatic patients and 28 controls. "TSST (toxic shock syndrome toxin) was detected in 47% (20/41) of cases and in 6% (1/28) of the controls with a significant difference. (P value = 0.000) Entrotoxins (A, B, D) were detected in the sera of 48.8% (21/41) of cases; and only 6 %( 1/21) of controls, showed significant differences (P value = 0.000) positive TSST was more common in spring, and correlates with CPP type of psoriasis, but not related to patient`s gender and age."

Atefi - Jundishapur J Microbiol 2014 full article / PubMed Central

Identification of Bacterial DNA in the Peripheral Blood of Patients With Active Psoriasis. A Ramírez-Boscá, V Navarro-López, A Martínez-Andrés, J Such, R Francés, J Horga de la Parte, M Asín-Llorca. JAMA Dermatol 2015 Jun;151(6):670-671. 54 patients with psoriasis and 27 controls. "Blood bactDNA was present in 16 patients with psoriasis, all of whom showed the phenotype of plaque psoriasis (16 of 45 [35.5%]), whereas 6 patients with guttate psoriasis, 3 with inverse psoriasis, and all 27 controls did not have bactDNA in the blood. Species identification corresponded to Escherichia coli (n = 9), Klebsiella pneumoniae (n = 2), Enterococcus faecalis (n = 2), Proteus mirabilis (n = 1), Streptococcus pyogenes (n = 1), and Shigella fresneli (n = 1)."

Ramírez-Boscá / JAMA Dermatol 2015 Research Letter

PCR investigation of Panton-Valentine leukocidin, enterotoxin, exfoliative toxin, and agr genes in Staphylococcus aureus strains isolated from psoriasis patients. Göçmen Jülide Sedef, N Sahiner, M Koçak, ZC Karahan. Turk J Med Sci 2015;45(6):1345-1352. "None of the strains isolated from the control group carried the agr locus. On the other hand, 11 of the S. aureus strains isolated from the patients carried type 1, 7 carried type 1 + 3, 4 carried type 2, 4 carried type 3, and 1 carried type 1 + 2 agr loci."

Göçmen Jülide Sedef - Turk J Med Sci 2015 abstract / PubMed

Frequency of streptococcal upper respiratory tract infections and HLA-Cw*06 allele in 70 patients with guttate psoriasis from northern Poland. A Maciejewska-Radomska, A Szczerkowska-Dobosz, K Rębała, J Wysocka, J Roszkiewicz, Z Szczerkowska, W Placek. Postepy Dermatol Alergol 2015 Dec;32(6):455-458. "HLA-Cw*06 allele was confirmed in 49 (70%) out of 70 patients, which is significantly higher than in the control population (30%) (p = 0.001). Evidence for streptococcal infection was found in 34 (48.5%) subjects with psoriasis. Twenty-seven of them (79%) carried HLA-Cw*06 allele. In 36 individuals in whom no evidence of streptococcal infection was found, 14 (39%) did not carry HLA-Cw*06 allele."

Maciejewska-Radomska - Postepy Dermatol Alergol 2015 full article / PubMed Central

Antibiotic Exposure, Infection, and the Development of Pediatric Psoriasis: A Nested Case-Control Study. DB Horton, FI Scott, K Haynes, ME Putt, CD Rose, JD Lewis, BL Strom. JAMA Dermatol 2016 Feb 1;152(2):191-199. 845 children with newly diagnosed psoriasis, 8450 controls. "After adjusting for matching, country, socioeconomic deprivation, outpatient visits, and infections within the past 2 years, antibiotic exposure in the last 2 years was weakly associated with incident psoriasis (adjusted odds ratio [aOR], 1.2; 95% CI, 1.0-1.5). The associations for infections of skin (aOR, 1.5; 95% CI, 1.2-1.7) and other sites (aOR, 1.3; 95% CI, 1.1-1.6) were similar. Untreated nonskin infections (aOR, 1.5; 95% CI, 1.3-1.8) but not antibiotic-treated nonskin infections (aOR, 1.1; 95% CI, 0.9-1.4) were associated with psoriasis."

Horton - JAMA Dermatol 2016 abstract / PubMed

Streptococcus pyogenes-induced cutaneous lymphocyte antigen-positive T cell-dependent epidermal cell activation triggers TH17 responses in patients with guttate psoriasis. E Ruiz-Romeu, M Ferran, M Sagristà, J Gómez, A Giménez-Arnau, K Herszenyi, P Hóllo, A Celada, R Pujol, LF Santamaria-Babí. J Allergy Clin Immunol 2016 Aug;138(2):491-499.e6. 14 patients, 6 healthy controls. "[A] higher TH17 response was observed in cells isolated from patients with flares associated with a streptococcal tonsillitis and with the HLA-Cw6 allele (cohort 1). In addition, in normal keratinocytes the supernatants from these cocultures induced an increase in IL-17-associated genes, such as DEFB4, S100A7, LCN2, IL36G, and IL8 but a decrease in FLG and LOR, thereby confirming the role of activated TH17 cells."

Ruiz-Romeu - J Allergy Clin Immunol 2016 abstract / PubMed

Throat Infections are Associated with Exacerbation in a Substantial Proportion of Patients with Chronic Plaque Psoriasis. RH Thorleifsdottir, JH Eysteinsdóttir, JH Olafsson, MI Sigurdsson, A Johnston, H Valdimarsson, B Sigurgeirsson. Acta Derm Venereol 2016 Aug 23;96(6):788-791. Survey of 275 psoriasis patients. "Of patients with plaque psoriasis, 42% reported sore throat-associated psoriasis exacerbations, and of patients with confirmed streptococcal infections, 72% reported aggravation. Notably, women and patients with early onset psoriasis were more likely to report psoriasis exacerbation after a sore throat (p < 0.001, p = 0.046, respectively)."

Thorleifsdottir - Acta Derm Venereol 2016 abstract / PubMed

HLA-Cw6 homozygosity in plaque psoriasis is associated with streptococcal throat infections and pronounced improvement after tonsillectomy: A prospective case series. RH Thorleifsdottir, SL Sigurdardottir, B Sigurgeirsson, JH Olafsson, H Petersen, Sigurdsson, JE Gudjonsson, A Johnston, H Valdimarsson. J Am Acad Dermatol 2016 Nov;75(5):889-896. 28 patients. "After tonsillectomy, HLA-Cw*0602 homozygotes showed significantly more improvement, compared with heterozygous and HLA-Cw*0602-negative patients... The homozygotes more often had psoriasis onset associated with a throat infection (P = .007) and an increased frequency of streptococcal throat infections per lifetime (P = .038)."

Thorleifsdottir - J Am Acad Dermatol 2016 abstract / PubMed

The psoriasis risk allele HLA-Cw0602 shows evidence of association with chronic or recurrent streptococcal tonsillitis. K Haapasalo, LLE Koskinen, J Suvilehto, P Jousilahti, A Wolin, S Suomela, R Trembath, J Barker, J Vuopio, J Kere, TS Jokiranta, P Saavalainen. Infect Immun 2018 Jul 23. pii: IAI.00304-18. "Genetic association between the cases and controls showed strongest association with two peaks in the HLA locus (OR 3.7-4.7, p=4.9-5.7x10-6). Further analysis with imputed classical HLA alleles suggested the known psoriasis risk allele HLA-C*06:02 as a risk factor for tonsillitis (p=4.8 x 10-4, OR 2.3). In addition, the imputed HLA haplotype HLA-C*06:02/HLA-B*5701, a reported risk haplotype in psoriasis, had the strongest risk for tonsillitis, too (p=8.0 x 10-3, OR 5.5)."

Haapasalo - Infect Immun 2018 abstract / PubMed

CMV is Also Involved

A high prevalence of cytomegalovirus antigenaemia in patients with moderate to severe chronic plaque psoriasis: an association with systemic tumour necrosis factor alpha overexpression. K Asadullah, S Prösch, H Audring, I Büttnerova, HD Volk, W Sterry, WD Döcke. Br J Dermatol 1999 Jul;141(1):94-102. "we frequently found CMV antigenaemia in psoriasis (43%) compared with healthy laboratory staff (12%, P < 0. 01) and blood donors (6%, P < 0.001). Clearance of CMV antigenaemia was observed with antipsoriatic treatment. CMV antigenaemia was symptomless, and was associated with seropositivity for anti-CMV IgG but not IgM antibodies, indicating subclinical activation of latent infection. Serological investigations in 85 psoriatic patients gave no evidence for a higher prevalence of latent CMV infection. In psoriatic lesions, CMV DNA was only rarely detected by polymerase chain reaction. As it has been shown that tumour necrosis factor (TNF)-alpha can induce CMV reactivation, we determined TNF-alpha plasma concentrations and mRNA expression in PBMC from psoriatic patients. Elevated TNF-alpha levels were found and correlated with the frequency of CMV antigen-expressing PBMC, suggesting a critical role of TNF-alpha in CMV activation."

Asadullah - Br J Dermatol 1999 abstract / PubMed

Cross-recognition of HLA DR4 alloantigen by virus-specific CD8+ T cells: a new paradigm for self-/nonself-recognition. M Rist, C Smith, MJ Bell, SR Burrows, R Khanna. Blood 2009 Sep 10;114(11):2244-2253. "Functional characterization of a human leukocyte antigen (HLA) Cw*0602-restricted cytomegalovirus-specific CD8(+) T-cell response revealed an unusual dual specificity toward a pp65 epitope and the alloantigen HLA DR4. This cross-recognition of HLA DR4 alloantigen was critically dependent on the coexpression of HLA DM and was preferentially directed toward the B-cell lineage. Furthermore, allostimulation of peripheral blood lymphocytes with HLA DRB*0401-expressing cells rapidly expanded CD8(+) T cells, which recognized the pp65 epitope in the context of HLA Cw*0602. T-cell repertoire analysis revealed 2 dominant populations expressing T-cell receptor beta variable (TRBV)4-3 or TRBV13, with cross-reactivity exclusively mediated by the TRBV13(+) clonotypes. More importantly, cross-reactive TRBV13(+) clonotypes displayed markedly lower T-cell receptor binding affinity and a distinct pattern of peptide recognition, presumably mimicking a structure presented on the HLA DR4 allotype." "Of the major subtypes of HLA DR4 tested, DRB*0401 and DRB*0408 were strongly recognized, whereas a lower level of recognition of DRB*0410 was also observed. In contrast, APCs expressing DRB*0402, DRB*0403, DRB*0404, DRB*0406, and DRB*0407 were not recognized."

Rist / Blood 2009 full article

Persistent CMV infection correlates with disease activity and dominates the phenotype of peripheral CD8+ T cells in psoriasis. M Weitz, C Kiessling, M Friedrich, S Prösch, C Höflich, F Kern, HD Volk, W Sterry, K Asadullah, WD Döcke. Exp Dermatol 2011 Jul;20(7):561-567. 29 patients with active plaque psoriasis and 29 healthy controls. "(i) Psoriasis severity was higher in CMV-seropositive patients and positively correlated to the severity of CMV-antigenaemia. (ii) In comparison to CMV-seropositive healthy controls, CMV-seropositive psoriasis patients showed a reduced frequency of circulating CMV-specific T cells that increased under effective antipsoriatic therapy. (iii) The immunophenotype of peripheral CD8+ T cells was dominated by CMV-seroprevalence. (iv) Selective analysis of CMV-seronegative psoriasis patients revealed a strong expansion of a - probably early activated - CD8+ T-cell population with the yet undescribed differentiation phenotype 'CD45RA-dim/CD11a-dim'. Under effective antipsoriatic therapy this population decreased in parallel to an increase of effector differentiated CD8+ T cells."

Weitz - Exp Dermatol 2011 abstract / PubMed

Psoriasis and Social Class

Impact of psoriasis severity on family income and quality of life. T Hawro, A Zalewska, M Hawro, A Kaszuba, M Królikowska, M Maurer. J Eur Acad Dermatol Venereol 2015 Mar;29(3):438-443. 83 Polish psoriasis patients. "Patients' family income correlate negatively with psoriasis severity (Spearman's rho = -0.356; P < 0.01). Disease severity in patients with a family income below the social minimum was significantly higher (PASI: 20.5 ± 12.2) than in patients with a higher family income (PASI: 11.7 ± 7.7, P < 0.001). We found that education, disease severity and age predict 50% of the variability in family income (P < 0.001). Disease severity showed the second strongest impact on income after education (P < 0.01). Family income was found to link disease severity to global QoL impairment (P < 0.05)."

Hawro - J Eur Acad Dermatol Venereol 2015 abstract / PubMed

See Also:


(Balancing selection and heterogeneity across the classical human leukocyte antigen loci: a meta-analytic review of 497 population studies. OD Solberg, SJ Mack, AK Lancaster, RM Single, Y Tsai, A Sanchez-Mazas, G Thomson. Hum Immunol 2008 Jul;69(7):443-464.)

HLA-Cw*0602 / Pypop Cw*0602 is common in Europe, Africa and the Middle East
DRB1*0401 / Pypop DRB1*0401 is most common among Beringia natives, and less common in northwest Europe

CMV Causes Rheumatoid Arthritis DRB1*0401 is part of the Shared Epitope by which CMV is implicated in RA
Group A streptococcus and children's behavior


cast 09-06-18