Association of psoriasis vulgaris with HLA class I and class II antigens in the Turkish population,according to the age at onset

BACKGROUND: Association of psoriasis vulgaris with HLA antigens reference to age at onset has been reported in different racial or ethnic populations. OBJECTIVE: Our purpose was to determine the distribution of HLA markers in the Turkish population according to the age at onset of the psoriasis vulgaris. METHODS: HLA class I and class II antigens were performed by serologic methods in a group of 100 Turkish patients with psoriasis and 201 control subjects. Patients with psoriasis were subdivided into two groups based on age at onset (below or above 40 years of age) and family history. RESULTS: The frequency of HLA A30, Cw3, Cw6, DR7, DR14, DQ8, and DQ9 antigens were significantly increased in the Turkish psoriatic patients whereas HLA A66, Cw2, Cw4 and DR11 were found to be negatively associated with psoriasis. However, there were striking differences in HLA antigens according to the age at onset of the disease. Type I, early onset was associated with a high frequency of A30, B50, Cw6 and DR7 antigens whereas patients with type II, late onset had an increased frequency of Cw7. CONCLUSIONS: We conclude that psoriasis is probably a genetically determined disease and suggest that HLA-Cw6 antigen seems to associate commonly with early onset of psoriasis in Turkish patients.     

Analysis of HLA antigens in Croatian patients with psoriasis

In common with most autoimmune diseases, psoriasis is associated with some HLA antigens. We studied the distribution of HLA antigens in Croatian patients with psoriasis: 108 patients were divided into groups according to family history and age of disease onset. HLA antigens were analyzed serologically and HLA-C alleles were analyzed using polymerase chain reaction. We found significant increases in HLA-A2, -B17, -B37 and -B13 antigens and highly significant increases in HLA-Cw*0602 and DR7 antigens in psoriatic patients compared with controls. Patients with type I psoriasis (early onset, positive family history) showed highly significant associations with Cw*0602 [p < 0.00001; relative risk (RR) = 14.45] and DR7 (p < 0.00001; RR = 15.09) antigens. Patients with type II psoriasis (late onset, no family history) had a significant association with Cw*03 antigen (p = 0.008; RR = 0.17). In conclusion, HLA-B13, -B17, Cw*0602 and -DR7 antigens are associated with a significant risk of psoriasis in the Croatian population and the Cw*0602 allele has the strongest association, especially for type I psoriasis.     

HLA polymorphism among Chinese patients with chronic plaque psoriasis: subgroup analysis

Background HLA‐Cw*06 has a strong influence on the clinical features and the susceptibility to psoriasis in different ethnicities. It is also used as a biomarker to predict the therapeutic efficacy of biologics, with inconsistent results. Additionally, most Asian patients with psoriasis do not carry HLA‐Cw*06. Objectives To determine additional HLA alleles which confer susceptibility or affect the severity of psoriasis in Chinese Han individuals. In addition, the potential of using HLA to predict treatment outcomes was also investigated. Methods We conducted a case–control association study in 199 Chinese patients with psoriasis and 200 unrelated healthy controls. HLA‐B and HLA‐C genotyping was performed and correlated with the therapeutic efficacy of the biologics, including alefacept, efalizumab, etanercept and ustekinumab. Patients with psoriasis were divided into group A (high‐need patients with moderate to severe psoriasis) and B (general patients with psoriasis). Results The frequencies of HLA‐B*60, HLA‐B*75, HLA‐Cw*06 and HLA‐Cw*10 were significantly increased in patients with psoriasis compared with the healthy controls. However, the prevalence of HLA‐Cw*06 was lower in group A compared with group B (6% vs. 17%, Pc = 0·04). HLA‐B*46 was found to be strongly associated with group A but not with group B patients with psoriasis. HLA‐Cw*01/HLA‐B*46 was also identified as a risk haplotype for Chinese patients with psoriasis, compatible with the results in Thais. Significant differences in response to biologics were observed between HLA‐Cw*01+ and HLA‐Cw*01? individuals in the alefacept treatment group, and between HLA‐B*37+ and HLA‐B*37?, and HLA‐B*58+ and HLA‐B*58? individuals in the efalizumab treatment group. Conclusions In addition to HLA‐Cw*06, the HLA‐Cw*01/HLA‐B*46 haplotype was also increased in Chinese patients with psoriasis. High‐need patients with psoriasis had a lower frequency of HLA‐Cw*06 but a higher prevalence of HLA‐B*46 compared with general patients with psoriasis in our population.     

Study of HLA class I,class II and complement genes (C2, C4A,C4B and BF) in Japanese psoriatics and analysis of a newly-found high-risk haplotype by pulsed field gel electrophoresis

Summary Genetic polymorphisms of HLA antigens and HLA-linked serum complement components (C2, C4A, C4B and BF) were investigated in 79 Japanese patients suffering from psoriasis. HLA typing revealed increased frequencies of HLA-A1, A2, B39, Bw46, Cw6, Cw7 and Cw11. Among complement components, positive associations were obtained with C4A4 and C4B2 and a negative association with BFF. The major histocompatibility complex haplotype (supratype), HLA-A2-Cw11-Bw46-C2C-BFS-C4A4-C4B2-DRw8 is purported to be a new high-risk haplotype in Japanese patients with psoriasis. Analysis of patients with this supratype via pulsed field gel electrophoresis showed the existence of specific, extensive DNA deletions near HLA-DR genes, but no disease-specific patterns could be observed by means of this technique. The newly-found high-risk haplotype indicates racial and ethnic differences among psoriatic patients.     

Human lymphocyte antigens A, B, and C in Greek patients with psoriasis: relation to age and clinical expression of the disease

The frequencies of human lymphocyte antigens (HLAs) A, B, and Cw6 were studied in a group of 212 Greek patients with psoriasis and 202 control subjects. An increased frequency of B13, B16, and Cw6 antigens and a low frequency of B14 were noted in the group of all patients. However, there were striking differences in HLA phenotypes according to the age at onset of the disease. Early onset (less than 25 years of age) was associated with a high frequency of A1, B17, B37, and Cw6 antigens, whereas patients with late onset (greater than 25 years of age) had a significantly lower incidence of A1, B17, and Cw6, which did not differ from that of the control subjects. Patients with onset of the disease greater than 60 years of age had, in addition, an increased frequency of B16. Psoriatic erythroderma was characterized by an increase of Aw19 and a higher frequency of B13 than in the total group of patients with psoriasis. In patients with a familial incidence of the disease, there was no significant association with any particular HLA.     

The frequency of QAP2.1 is increased in psoriasis vulgaris patients but no unusual linkage between QAP/DQA1 or QBP/DQB1

Psoriasis vulgaris is a chronic skin disease with a genetic and immunological background. We have previously defined the two most frequent risk haplotypes in Finns: A2,B13,Cw6,DR7,DQA1*0201 and A1,B17,Cw6,DR7,DQA1*0201. The aim of this study was to further examine whether the flanking regions, URRs of DQ (QAP and QBP) and TAP1 and TAP2 genes are involved in susceptibility to psoriasis. The frequency of QAP2.1 was increased in psoriatics as compared with controls ( P _c = 3.6 × 10 ^–2 , RR = 5.0), and the frequency of QAP4.1 was decreased in psoriasis patients ( P _c = 4.2 × 10 ^–2 ). The frequency of the phenotype combination Val/Ile at position 379 of TAP2 was decreased in patients ( P _c = 1 × 10 ^–2 ). The allele and phenotype frequencies of TAP1 and TAP2 genes were not different between these groups. Haplotypes A2, B13,Cw6,DR7,DQA1*0201,QAP2.1 and A1,B17,Cw6, DR7,DQA1*0201,QAP2.1 are the two most frequent HLA marker haplotypes for psoriasis vulgaris in Finns, Cw6, DR7, DQA1*0201 and QAP2.1 being the most important single alleles for the risk of this disease. Received: 1 July 1996     

HLA-class 1 and class 2 antigens in Turkish patients with pemphigus

BACKGROUND: Pemphigus is an autoimmune disease which is more frequently seen in certain ethnic groups such as Jews. It is thought that exogenous factors may induce pemphigus in genetically predisposed individuals. Recent reports on HLA antigens indicate an increased frequency of HLA-class II antigens particularly HLA-DR4 among Jewish patients. Herein we investigated the antigen frequencies of HLA-A, B, C, HLA-DR and DQ in Turkish patients with pemphigus. METHODS: HLA class I and II antigens were typed by microdroplet lymphocyte cytotoxicity test in 33 patients with pemphigus and 100 healthy individuals. RESULTS: HLA-B35, B44, CW4, DR4, DR14, DQ8 and DQ4 antigens were significantly high in the study group whereas HLA-DR11, DQ7 and DQ2 antigens were high among the controls. The most striking differences were observed in HLA class II antigens. HLA DR14-DQ8 and HLA B35-DR14 haplotypes were the most frequently observed ones in the study group. CONCLUSIONS: We postulate that HLA-B35, B44, CW4, DR4, DR14, DQ4 and DQ8 antigens may be responsible for susceptibility to pemphigus while HLA-DR11, DQ7 and DQ2 antigens may have a protective role in the Turkish population.     

Association of HLA-A, -B, -C genes and TNF microsatellite polymorphism with psoriasis vulgaris: a study of genetic risk in Brazilian patients

This study investigated the genetic association of HLA class I genes and TNF-alpha microsatellites. HLA-A, -B, -C typing was carried out in 92 psoriasis vulgaris patients and 160 healthy individuals using a PCR-SSP method. 70 patients and 71 controls were typed for five microsatellite polymorphisms, TNFa-e. HLA-B*13 Cw*06, HLA-B*57 Cw*06 and HLA-B*39 Cw*12 haplotypes were found to be increased in patients with psoriasis type I when compared to controls, which could determine the susceptibility to development of psoriasis. TNFa4, TNFb1, TNFe1 and TNFa2 b1 c2 d4 e1 haplotypes showed a decreased frequency (p < 0.05) in psoriasis patients when compared to controls. HLA-B*13 allele and HLA-B*13 Cw*06, TNFa11 b4 c1 d3 e3 haplotypes showed increased frequencies (p < 0.05) in patients with type II psoriasis, which suggests susceptibility to the onset of psoriasis. Our results detected polymorphisms of the HLA class I and microsatellite TNF locus which could be markers of genetic predisposition to the disease.     

HLA C and D antigens associated with psoriasis

The frequency of two newly defined HLA antigens, HLA CT7 and DMA, was found to be greatly increased in patients with psoriasis. These two antigens and those previously found to be associated with the disease, B13, BW16 and BW17, frequently occurred together. The disease may be primarily associated with HLA DMA, or with the HLA haplotypes CT7--B13/W16/W17--DMA.     

Associations between human leukocyte antigens and leprosy in the Turkish population

Leprosy is a chronic infection caused by an intracellular microorganism. Genetic predisposition to both disease susceptibility and to host immunological response has been postulated for many years. The aim of this study was to determine whether there is HLA-linked susceptibility to leprosy and its different types. HLA-class I (A, B, C) and II (DR, DQ) antigen frequencies in 80 patients with leprosy (35 borderline lepromatous, 25 lepromatous, 15 borderline tuberculoid, five tuberculoid) were compared with those in 120 healthy individuals. HLA-class I antigens A9, A10, A32, B5, B21, Bw4, Bw6, Cw1, Cw2 and HLA-class II antigens DR9, DR10, DRw52, DQ1, DQ3 were found to be significantly more frequent in patients with leprosy, whereas HLA-class I antigens A3, B44, B49 and HLA-class II antigen DQ5 were so in controls. However, there was no significant difference in HLA-class I and II antigen frequencies between subtypes of leprosy. HLA-A null antigen was found to have weak expression in patients with leprosy. In conclusion, factors other than HLA-class I and class II antigens may have a more critical role in the pathophysiology of leprosy infection in man.     

The major histocompatibility complex in psoriasis vulgaris. III. HLA-C antigens.

HLA-C typing was performed on 40 unrelated Japanese patients with psoriasis vulgaris. The patient group consisted of 22 patients who had psoriatic HLA antigens i.e., B13 in seven cases, B17 in one case and B37 in 14 cases; and 18 patients who had none of these specific HLA antigens. HLA-C typing was also performed on 40 unrelated healthy Japanese controls. Cw6 was found in 55.0% of the patients as compared with 5.0% of the healthy controls. All patients (21 cases) who had either B13 or B37 were positive for Cw6. Both controls who were positive for Cw6 also had B37. These results suggest the possibility of a linkage disequilibrium between Cw6 from locus C and B13 and B37 from locus B, and/or an association between Cw6 and susceptibility to psoriasis.     

Immunogenetic profile of psoriasis vulgaris: Association with haplotypes A2, B13,Cw6,DR7,DQA1*0201 and A1,B17,Cw6,DR7,DQA1*0201

Psoriasis vulgaris is a skin disease with an immunological and genetic background present in 1–3% of the population. We studied the genetic susceptibility to psoriasis vulgaris in Finns with serological HLA typing and genomic HLA class II typing of the DQ and DP loci to evaluate the risk of developing psoriasis. The haplotypes most frequently distinguishing between psoriatics and controls were those that carried Cw6 ( P < 10 ^–8 ), DQA1*0201 ( P = 9.3 × 10 ^–6 ) and DR7 ( P = 3.9 × 10 ^–5 ). The two most frequent marker haplotypes were A2,B13,Cw6,DR7,DQA1*0201 and A1,B17,Cw6,DR7,DQA1*0201, which were not found among the control subjects. A deficit of haplotype B8,DR3,DQ2 (2 out of 124 in the patients versus 15 out of 106 in the controls, P = 1.5 × 10 ^–4 ) was found, and this was in accordance with a slightly decreased frequency of DQA1*0501 ( P = 3.1 × 10 ^–2 ), which was usually linked with this haplotype. These results stimulate the search for a genetic resistance factor in psoriasis. Thus, this report sheds further light on the immunogenetic background of psoriasis in Finland. We conclude that the inheritance of psoriasis has a polygenic mode, in which the Cw6,DR7,DQA1*0201 combination seems to be important ( P = 7.5 × 10 ^–7 , relative risk 24.4, aetiological factor 0.29). Received: 6 December 1994     

河南地区汉族人银屑病与HLA—Cw0602等位基因的关联研究

目的：分析河南地区汉族人银屑病与HLA—Cw＊0602等位基因的相关性。方法：运用聚合酶链反应一序列特异性引物（PCR—SSP）法检测河南地区汉族人200例寻常型银屑病患者和200名健康对照的HLA—Cw＊0602等位基因频率,并分析携带该基因的银屑病患者与家族史的关系。结果：病例组HLA—Cw＊0602等位基因频率较对照组显著升高（73％VS24％,P=0．000）,但无性别差异;携带HLA—Cw＊0602等位基因的银屑病患者发病年龄早于不具有该等位基因的患者（80．2％VS28．6％,P=0．001）;有银屑病家族史患者携带HLA—Cw＊0602等位基因的频率与无银屑病家族史者差异无显著性（P=1．000）。结论：HLA—Cw＊0602等位基因与河南地区汉族人银屑病易感性高度关联。携带该等位基因的银屑病患者易为早发型,但不能确定有家族倾向性。     

HLA-A, -B and DR antigens in nickel sensitive females

The relationship between HLA antigens (A, B and DR) and nickel contact sensitivity was examined in a series of 26 female patients with unequivocal positive patch-test reactions to nickel. A comparison of patient antigen frequency versus Yorkshire Region HLA antigen figures showed an increased incidence of HLA-B35 in our patient population, (P < 0.01). The relative risk (RR) for the development of nickel sensitivity was reflected in the increased values for HLA-B35 and BW22 in our patients when compared with Yorkshire frequencies. We found no significant association between DR antigens and RR in our patients. The aetiological fraction (EF) showed no significant association between HLA antigens and nickel contact sensitivity.     

Salient features and HLA markers of childhood psoriasis in Kuwait

A total of 305 consecutive Kuwaiti children with psoriasis were studied for clinical features and 50 children were tissue typed for HLA class I and class II antigens. The salient features of psoriasis in these children included: female preponderance (M : F ratio, 1:1.5); peak age of onset between 2 and 8 years; scalp as the most common site of onset (30%); scalp and extensors of legs as commonly affected sites (52.5% each); plaque psoriasis the most common clinical type (89%); and a positive family history of psoriasis in 34% of the patients. Kuwaiti children with psoriasis showed a significant association with HLA-A3, Cw1, and DR7 antigens and those with a positive family history of psoriasis had a significant association with HLA-DR8 antigen.     

HLA‐Cw6 and psoriasis

Psoriasis is a multifactorial disease with a strong genetic background. HLA‐Cw6 is one of the most strongly associated psoriasis susceptibility alleles. It is repeatedly observed to affect disease course, phenotypic features, severity, comorbidities and treatment outcomes. To the best of our knowledge, the roles of HLA‐Cw6 in psoriasis have not yet been thoroughly reviewed. The worldwide frequency of the HLA‐Cw6 allele varies greatly, with it being generally higher in white people than in Asians. The allele is associated with type I early‐onset psoriasis. Stress, obesity and streptococcal pharyngitis are commonly observed in HLA‐Cw6‐positive patients. Phenotypically, HLA‐Cw6 has been found to be associated with guttate psoriasis. In addition, patients carrying the allele are more likely to have arm, leg and trunk involvement, and the Koebner phenomenon. Patients with psoriatic arthritis with HLA‐Cw6 more often have early onset and tend to show cutaneous symptoms before musculoskeletal symptoms. HLA‐Cw6‐positive patients have been shown in several studies to be more responsive to methotrexate and ustekinumab. However, this difference in ustekinumab efficacy was only moderate in a post‐hoc analysis of a pivotal phase III study. HLA‐Cw6 positivity also tends to be less frequent in high‐need patients who fail conventional therapy. Small studies have also investigated the role of HLA‐Cw6 in remission of psoriasis during pregnancy, and with the comorbidities of photosensitivity and atherosclerosis. Given the diverse nature of psoriasis pathogenesis, as well as the difference of HLA‐Cw6 positivity in different ethnic groups, more studies are needed to confirm the role of HLA‐Cw6 in psoriasis.     

Psoriasis vulgaris and human leukocyte antigens

BACKGROUND: Psoriasis vulgaris is a skin disease with a complex immunological and genetic background, triggered by environmental factors. The association of human leukocyte antigens (HLA) and psoriasis has long been reported on population and familial studies. OBJECTIVES: To review and discuss studies on psoriasis vulgaris and HLA, in Caucasian and non-Caucasian populations. METHODS: The major population studies on psoriasis vulgaris and the associated HLA antigens and alleles are described and discussed based on a review of the current literature. RESULTS: Population studies demonstrate the presence of different HLA specificities as well as extended haplotypes in patients with psoriasis, when compared to controls. Some alleles occur in a lower frequency in patients with psoriasis, indicating they could be protection alleles. In all studies which HLA class I was typed, Cw6 or Cw*0602 was present in a significant frequency in patients with psoriasis, mainly when early onset and positive family history were considered. HLA-DRB1*0701 was also present in a higher frequency in patients in different populations. CONCLUSIONS: Different antigens and alleles from both HLA classes I and II were seen in a significantly higher frequency in patients with psoriasis vulgaris. HLA Cw*0602 and DRB1*0701 were represented in different reports, and the former was related mainly to psoriasis type I.     

Specific restriction fragment length polymorphism on the HLA-C region and susceptibility to psoriasis vulgaris

In psoriasis vulgaris, the HLA class I Cw6 specificity has previously been recognized as the most commonly associated antigen serologically. This study was carried out to investigate whether or not the gene controlling the susceptibility to psoriasis vulgaris existed on the HLA, especially the HLA-C region. At first, we analyzed the restriction fragment length polymorphism (RFLP) of 13 patients with psoriasis vulgaris and 6 healthy controls who were all positive for at least one allele of HLA-Cw6. To characterize RFLP in psoriasis patients who did not have HLA-Cw6, 12 patients and 10 healthy controls who had HLA-Cw7 were also examined. Southern hybridization of genomic DNA demonstrated that DNA polymorphisms of the HLA-C antigen gene could not be found in any psoriasis vulgaris patient whether HLA-Cw6 or Cw7. However, a 4.5 kb BamHI fragment and a 3.1 kb PstI fragment were lacking in some healthy controls who had either HLA-Cw6 or Cw7. This study suggests that the presence of RFLP in the HLA-C gene is associated with psoriasis vulgaris. These specific fragments may help predispose individuals to psoriasis vulgaris, or may be essential for the development of the disease.     

The occurrence of various collagen diseases in one family: a sister with ISSc, PBC, APS, and SS and a brother with systemic lupus erythematosus.

We encountered siblings who had collagen diseases and related symptoms. Case 1 was a 53‐year‐old woman who had limited cutaneous systemic sclerosis (ISSc) associated with primary biliary cirrhosis (PBC), antiphospholipid antibody syndrome (APS), and subclinical Sjögren's syndrome (SS). Case 2 was a 48‐year‐old man, her younger brother, with systemic lupus erythematosus (SLE) that developed at 32 years of age. Investigation of their family revealed that their mother had Raynaud's phenomenon, arthritis, and subclinical Sjögren's syndrome, and that another younger brother of Cases 1 and 2 had Raynaud's phenomenon and general fatigue. HLA analysis revealed that the sister and brother had some identical HLA antigens in common, including A2, A33 (19), B67, B44 (12), Cw7, DR2, DR6, DR52, and DQ1. The sister, brother and their mother had common HLA antigens including A2, B67, Cw7, DR2, and DQ1. Although Cases 1 and 2 shared the same HLA system, they presented different phenotypes of collagen disease.     

Two sisters with impetigo herpetiformis

Two sisters (non-twins) had impetigo herpetiformis triggered by their first pregnancy. One sister treated with etretinate had good resolution of skin disease. Impetigo herpetiformis is probably a variant of pustular psoriasis and may be provoked or precipitated by factors, such as pregnancy. Both patients shared common HLA antigens (All, AW24, BW44, BW54 and DR6Y).