HLA-Cw6-positive patients with psoriasis show improved response to methotrexate treatment.

It is well documented that patients with human leucocyte antigen (HLA)-Cw6+ (type 1) psoriasis have increased severity and reduced age of onset of psoriasis. However, not much is known about any differential response of this genetic subgroup to various treatments. We set out to determine if there was any genetic association of the HLA-Cw6 allele with the first-line systemic treatment commonly used in psoriasis, methotrexate. A cohort of patients from Tayside in Scotland was recruited through a novel generic consenting process (GoShare); they were extensively phenotyped and analysed for an association of their HLA-Cw6 genotype status with treatment outcomes. HLA-Cw6+ patients showed notably improved response to methotrexate (P = 0.05), and further analysis demonstrated an even greater response in a subcohort of the HLA-Cw6+ patients, who did not have concomitant psoriatic arthritis (P = 0.01). HLA-Cw6+ patients also exhibited fewer treatment-limiting adverse events. In addition to these findings, the methodology and primary clinical outcome phenotype, which we validate here, will greatly facilitate replication of the present results in independent cohorts.

Matching at Human Leukocyte Antigen-C Improved the Outcomes after Double Umbilical Cord Blood Transplantation for Recipients of Two to Four of Six Human Leukocyte Antigen-Matched Grafts.

We studied the effect of HLA-C matching in 515 patients after double umbilical cord blood (UCB) transplantation. After HLA matching HLA-A, -B, and -DRB1 at the allele level, we scored patients according to number of donor-recipient HLA-C matches at 4 possible loci: 2 from each donor unit, at the allele level. Given a direct interaction between HLA-A, -B, and -DRB1 matching and HLA-C score, we analyzed HLA-C matching in those receiving at least 1 2/6 to 4/6 HLA-matched unit (n = 389) versus those receiving only 5/6 or 6/6-matched units (n = 126). In those with at least 1 2/6 to 4/6 HLA-matched unit, a better HLA-C matching score was associated with significantly lower risk of death of any cause and nonrelapse mortality and better disease-free survival. There was no association with the risk of relapse, acute and chronic graft-versus-host disease, and hematopoietic recovery. In contrast, among patients receiving only allele-level 5/6 or 6/6 HLA-matched UCB units, HLA-C match had no demonstrable effect on any outcome. For patients receiving at least 1 allele-level 2/6 to 4/6 HLA-matched UCB unit, matching at HLA-C reduces nonrelapse mortality and improves survival.

Expression of KIR2DS1 by decidual natural killer cells increases their ability to control placental HCMV infection.

The combination of the activating killer cell Ig-like receptor 2DS1 (KIR2DS1) expressed by maternal decidual natural killer cells (dNK) and the presence of its ligand, the HLA-C allotype HLA-C2, expressed by fetal trophoblasts, reduces the risk of developing pregnancy complications. However, no molecular or cellular mechanism explains this genetic correlation. Here we demonstrate that KIR2DS1+ dNK acquired higher cytotoxic function than KIR2DS1- dNK when exposed to human cytomegalovirus (HCMV)-infected decidual stromal cells (DSC), particularly when DSCs express HLA-C2. Furthermore, dNK were unable to degranulate or secrete cytokines in response to HCMV-infected primary fetal extravillous trophoblasts. This emphasizes the immunological challenge to clear placental viral infections within the immune-privileged placenta. Activation of dNK through KIR2DS1/HLA-C2 interaction increases their ability to respond to placental HCMV infection and may limit subsequent virus-induced placental pathology. This mechanism is directly related to how KIR2DS1 expressed by dNK reduces development of severe pregnancy complications such as miscarriages and preterm delivery.

HLA-Cw polypmorphism and killer cell immunoglobulin-like receptor (KIR) gene analysis in Korean colorectal cancer patients.

PURPOSE: Natural killer cells (NK cells) play important roles in protecting the patient from the early development of cancers, and are activated or inhibited by killer cell immunoglobulin-like receptors (KIR), which bind to HLA class I. In the present study, we investigated the KIR genotype of Korean colorectal cancer patients. METHODS: DNA samples were extracted from peripheral blood cell samples taken from Korean colorectal cancer patients and a control group. KIR genes were amplified using PCR-SSP methods, and HLA-Cw genes were characterized using PCR methods. The results were analyzed to assess the difference between colorectal cancer patients and the normal control group. RESULTS: In the present study, the frequency of KIR2DS5 (33.2% vs. 20.8%, p-value < 0.007) was higher in the colorectal cancer group, and in the rectal cancer subgroup, the frequencies of KIR3DL1 (93.2%, vs. 98.1%, p-value < 0.05), KIR2DS2 (7.8% vs. 19.5%, p-value < 0.01), and KIR2DS4 (93.2% vs. 98.1%, p-value < 0.05) were lower significantly. The frequencies of HLA-Cw6 (9.1% vs. 15.7%, p-value < 0.05) and HLA-Cw7 (17.4% vs. 27.7%, p-value < 0.02) were lower in the colorectal cancer group. Of the patients with HLA-C1 homozygote, the frequency of KIR2DS2 was decreased significantly (5.8% vs. 14.5%, p-value < 0.004). CONCLUSIONS: The frequency of KIR2DS5 is higher in Korean colorectal cancer patients, and in the rectal cancer subgroup, the frequencies of KIR3DL1, KIR2DS2 and KIR2DS4 are lower. Among the patients with HLA-C1 homozygote, the frequency of KIR2DS2 is decreased. Therefore, KIR2DS2 in presence of its ligand (HLA-C1 group) may have a protective effect against colorectal cancer.

Human leukocyte antigen-B (-Bw6/-Bw4 I80, T80) and human leukocyte antigen-C (-C1/-C2) subgrouping using pyrosequence analysis.

Specific combinations of killer immunoglobulin-like receptors (KIR) and human leukocyte antigen (HLA) class I molecules characterized by a particular residue 80 are significantly associated with outcomes in different pathologic conditions, such as autoimmunity, pathogenic infection, cancer, and reproductive failure. Thus, a simplified method for HLA typing used in association with the analysis of KIR genotype (Kirotype) is of particular interest to extend the analysis of larger series. Here, we describe a quick and inexpensive method that allows use of pyrosequencing, a helpful subtyping of HLA class I molecules, into HLA-Bw6, -Bw4 I(80) or -Bw4 T(80), HLA-C1, or -C2 groups and HLA-A allotypes sharing Bw4+ epitope or the rare HLA-B allotypes displaying the C1 motif. In particular, this analysis is focused on the amino acids around residue 80, known to be relevant in defining the affinity of KIR/HLA interaction and in the functional effects. This method was demonstrated to have good sensitivity, specificity, and reproducibility of detection and it was validated using a panel of HLA-typed International Histocompatibility Workshop (IHW) cell lines and clinical isolates. Using an allele quantitative acquisition mode, the method permitted us to obtain an accurate sequencing as required in heterozygous and/or homozygous sample definition.

Abnormality of RUNX1 signal transduction in psoriatic CD34+ bone marrow cells.

BACKGROUND: Although it has been shown that T-cell dysfunction in psoriasis correlates with various endogenous and exogenous stimuli, there are also intensive and complicated genetic background effects indicating that intrinsic abnormalities may play a more predominant role such as in haematopoietic cells, the haematopoietic microenvironment and the development of haematopoietic cells into T cells. OBJECTIVE: To reveal the activity of haematopoietic stem cells from patients with psoriasis. METHODS: Bone marrow CD34+ cells were isolated and expression levels were tested by reverse transcriptase-polymerase chain reaction and Western blotting. The binding site for RUNX1 located between SLC9A3R1 and NAT9 and the apoptotic index of CD34+ cells were also investigated. RESULTS: We found that the expression of RUNX1, SLC9A3R1, HLA-C and PRKCB mRNA and RUNX1 protein was significantly higher in patients with psoriasis than in the controls, and SLC9A3R1 expression showed a significant positive correlation with the Psoriasis Area and Severity Index score. There was no statistical significance for PDCD1 mRNA and PKC-ß I protein expression levels between the patients with psoriasis and controls. Mutation of RUNX1 binding sites between SLC9A3R1 and NAT9 was not detected, and the apoptotic index in patients with psoriasis showed no statistical significance compared with the controls. CONCLUSION: Expression of the critical transcription factor RUNX1, which regulates CD34+ cell development and differentiation, was abnormal, and augmentation of these expression levels might induce dysfunction of marrow haematopoietic stem cells and the haematopoietic microenvironment and be involved in the progression of psoriasis.

Analysis of HLA-ABC locus-specific transcription in normal tissues.

We developed a novel human leukocyte antigen HLA-ABC locus-specific quantitative real-time polymerase chain reaction (PCR) to determine the locus-specific gene expression of HLA-ABC in peripheral blood leukocytes (PBLs, n = 53), colon mucosa (n = 15), and larynx mucosa (n = 15). Laser-assisted tissue microdissection allowed us to study the selected cells without interference from surrounding stroma. We report evidence on the specificity of the technique, describing the HLA-ABC locus-specific gene expression patterns found in the PBLs and two solid tissues studied. PBLs showed a higher gene expression of HLA-B than of HLA-A or HLA-C (p = 4.7 × 10(-10) and p = 1.6 × 10(-6), respectively). In solid tissue, HLA-A and HLA-B gene expressions were similar and HLA-C expression lower. In particular, in larynx mucosa, significant differences were found between HLA-A and HLA-C expressions and between HLA-B and HLA-C expressions (p = 6.5 × 10(-4) and p = 8.1 × 10(-4), respectively). The same differences were observed in colon mucosa, but significance was not reached (p = 0.08 and p = 0.06, respectively). Differences in locus-specific regulation may be related to the control of cytotoxic responses of NK and CD8 positive T cells. Gene expression of HLA-ABC specific locus showed no intra-individual variability, but there was a high inter-individual variability. This may result from differences in the expression of common regulatory factors that control HLA-ABC constitutive expression.

An improved strip FRAP method for estimating diffusion coefficients: correcting for the degree of photobleaching.

Fluorescence recovery after photobleaching is a widely established method for the estimation of diffusion coefficients, strip bleaching with an associated recovery curve analysis being one of the simplest techniques. However, its implementation requires near 100% bleaching in the region of interest with negligible fluorescence loss outside, both constraints being hard to achieve concomitantly for fast diffusing molecules. We demonstrate that when these requirements are not met there is an error in the estimation of the diffusion coefficient D, either an under- or overestimation depending on which assumption is violated the most. We propose a simple modification to the recovery curve analysis incorporating the concept of the relative bleached mass m giving a revised recovery time parametrization tau=m(2)w(2)/4piD for a strip of width w. This modified model removes the requirement of 100% bleaching in the region of interest and allows for limited diffusion of the fluorophore during bleaching. We validate our method by estimating the (volume) diffusion coefficient of FITC-labelled IgG in 60% glycerol solution, D= 4.09 +/- 0.21 microm(2) s(-1), and the (surface) diffusion coefficient of a green-fluorescent protein-tagged class I MHC protein expressed at the surface of a human B cell line, D= 0.32 +/- 0.03 microm(2) s(-1) for a population of cells.

Placental pathology in egg donor pregnancies.

OBJECTIVE: To determine placental pathology and immune response at the maternal-fetal interface in pregnancies conceived by IVF via egg donation compared with nondonor IVF pregnancies. DESIGN: Retrospective case-control study. SETTING: Academic medical center. PATIENT(S): The study population included 20 egg donor and 33 nondonor IVF pregnancies of >24 weeks' gestation. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Perinatal complications (gestational hypertension, abruption, preterm delivery, cesarean section), microscopic features indicating an immune response and trophoblast damage, and characterization of inflammatory cells using immunohistochemistry. RESULT(S): There was an increase in gestational hypertension and preterm delivery in egg donor pregnancies. Dense fibrinoid deposition in the basal plate with severe chronic deciduitis containing significantly increased numbers of T helper and natural killer cells were demonstrated in egg donor placentas. Trophoblast damage was also increased in the preterm egg donor group. CONCLUSION(S): There are significant histological and immunohistochemical differences between the placentas of egg donor and nondonor IVF pregnancies. The increased immune activity and fibrinoid deposition at the maternal-fetal interface of egg donor pregnancies could represent a host versus graft rejection-like phenomenon.

Biological characteristics of dendritic cells derived from peripheral blood of patients with epithelial ovarian cancer.

BACKGROUND AND OBJECTIVE: Dendritic cells (DCs) are thought to be the most potent antigen-presenting cells (APC) and play a vital role in stimulating human immune response against cancer. At present, most data concerning the immuno-biological function of DCs are obtained from healthy donors. The information about the biological characteristics of DCs from patients is limited. In this study, the biological characteristics of monocyte-derived dendritic cells (MoDCs) from patients with ovarian cancer were investigated. METHODS: Monocytes were isolated from peripheral blood mononuclear cells (PBMC) of eight epithelial ovarian cancer patients and 13 healthy women volunteers, cultured with interleukin 4 (IL-4) and granulocyte-macrophage colony stimulating factor (GM-CSF), and stimulated with tumor necrosis factor-alpha (TNF-alpha). At seven days after induction, the morphologic characteristics of MoDCs were observed. The features of phenotype were analyzed using flow cytometry. The ability of MoDCs to stimulate proliferation of lymphocytes was tested by allogeneic mixed leukocytes reaction (MLR). RESULTS: Mature MoDCs with typical morphology were obtained after seven days of culture. MoDCs from both patients and healthy women expressed high levels of HLA-ABC (MHC-I), HLA-DR (MHC-II) and large amounts of CD86 and CD80. There was no significant differences between MoDCs from ovarian cancer women and healthy women in the mean fluorescence intensity (MFI) of HLA-ABC, HLA-DR, CD86 and CD80 (p > 0.05). The MLR was significantly weaker in ovarian cancer patients than in healthy women (p < 0.05). CONCLUSION: MoDCs from ovarian cancer patients may present lower capacity of stimulating proliferation of lymphocytes, indicating that the patients' MoDCs may have immunological function defect at certain extent.

Association of killer cell immunoglobulin-like receptors with primary Sjogren's syndrome.

OBJECTIVE: SS is a chronic inflammatory condition characterized by systemic and tissue-specific autoimmune features. In view of recent findings indicating a role for killer cell immunoglobulin-like receptors (KIRs) in the pathogenesis of other autoimmune rheumatic disorders such as SSc, and the autoimmune disorders RA and PsA, we sought to determine whether KIRs predict general or specific susceptibility in SS. METHODS: Eleven separate KIR genes were typed using PCR sequence-specific primers on genomic DNA from 72 patients diagnosed with primary SS and a control panel consisting of 223 blood donors. RESULTS: We found no individual KIR genes to be associated with SS. In contrast, 11 patients with primary SS (15%) and 9 control blood donors (4%) had KIR genotypes with the activating KIR2DS2 in the absence of its corresponding inhibitory homologue KIR2DL2 (P = 0.01). Further analysis of these individuals showed that seven SS patients were positive for HLA-C ligand for KIR2DS2 only compared with one control sample (P = 0.00026). CONCLUSION: The genetic combination of KIR2DS2+ and KIR2DL2- in the presence of HLA-C ligand specific for activating KIR2DS2 is associated with primary SS. This implies that autologous KIR-ligand interaction is a contributory factor to predisposition for this disease.

Comprehensive analysis of HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 loci and squamous cell cervical cancer risk.

Variation in human major histocompatibility genes may influence the risk of squamous cell cervical cancer (SCC) by altering the efficiency of the T-cell-mediated immune response to human papillomavirus (HPV) antigens. We used high-resolution methods to genotype human leukocyte antigen (HLA) class I (A, B, and Cw) and class II (DRB1 and DQB1) loci in 544 women with SCC and 542 controls. Recognizing that HLA molecules are codominantly expressed, we focused on co-occurring alleles. Among 137 allele combinations present at >5% in the case or control groups, 36 were significantly associated with SCC risk. All but one of the 30 combinations that increased risk included DQB1*0301, and 23 included subsets of A*0201-B*4402-Cw*0501-DRB1*0401-DQB1*0301. Another combination, B*4402-DRB1*1101-DQB1*0301, conferred a strong risk of SCC (odds ratio, 10.0; 95% confidence interval, 3.0-33.3). Among the six combinations that conferred a decreased risk of SCC, four included Cw*0701 or DQB1*02. Most multilocus results were similar for SCC that contained HPV16; a notable exception was A*0101-B*0801-Cw*0701-DRB1*0301-DQB1*0201 and its subsets, which were associated with HPV16-positive SCC (odds ratio, 0.5; 95% confidence interval, 0.3-0.9). The main multilocus associations were replicated in studies of cervical adenocarcinoma and vulvar cancer. These data confirm that T helper and cytotoxic T-cell responses are both important cofactors with HPV in cervical cancer etiology and indicate that co-occurring HLA alleles across loci seem to be more important than individual alleles. Thus, certain co-occurring alleles may be markers of disease risk that have clinical value as biomarkers for targeted screening or development of new therapies.

Synovitis-acne-pustulosis-hyperostosis-osteitis syndrome and psoriatic arthritis exhibit a different immunogenetic profile.

BACKGROUND AND OBJECTIVES: Patients with psoriatic arthritis (PsA) as well as those with synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome share some common features, and in fact, for many authors the SAPHO concept fits well into the broader concept of PsA. However, some clinical features are unique to the SAPHO syndrome, and in the other hand, these patients do not show the known association between the HLA-B27 antigen and the spondyloarthropathies. To date, there are no studies comparing the immunogenetic profile of these two conditions, so the main objective of the present report was to analyse whether or not both entities may share the same genetic basis. PATIENTS AND METHODS: All patients with SAPHO syndrome (n=25) seen in a single university hospital from 1985 to 2005 were recruited and followed up in standardised manner in order to study their main characteristics and HLA profile. The HLA-Cw6, DR and B27 antigen distribution of these cases was compared to that of 50 patients with psoriasis vulgaris, 120 with PsA, and 170 healthy blood donors. PsA patients were classified in accordance with their predominant pattern observed in the last 5 years of disease evolution. Odds ratios (OR) values were calculated to measure the strength of the association between HLA antigens and disease, while the statistical significance of the association was assessed with a two-tailed Fisher's exact test. P<0.05 values were considered significant. RESULTS: No association was found between HLA-Cw6, B27, or DR antigens, and SAPHO syndrome. HLA-Cw6 was strongly associated with psoriasis, OR 12 (95% CI: 5.6-26, p<0.0001) and PsA, OR 10 (95% CI: 5.4-19.5, p<0.0001), however this antigen was equally distributed among the three articular categories of PsA. HLA-DR4 was found under-represented in PsA patients compared to controls, OR 0.4 (95% CI: 0.2-0.7, p=0.002). HLA-DR7 correlated well with psoriatic oligoarthritis, OR 9.6 (95% CI: 2.9-28, p<0.0001), HLA-DR8 was found associated with polyarthritis, OR 6.7 (95% CI: 2-25, p=0.002), while HLA-B27 was over-represented in psoriatic spondylitis, OR 10 (95% CI: 3.3-25, p<0.0001). CONCLUSIONS: Psoriasis/PsA and SAP-HO syndrome show a different immunogenetic background, however the genetic basis of SAPHO syndrome remains unknown.

Are there common human leucocyte antigen associations in juvenile idiopathic arthritis and periodontitis?

AIM: The aim of this study was to evaluate common human leucocyte antigen (HLA) associations in patients with juvenile idiopathic arthritis (N=110), in patients with generalized aggressive periodontitis (N=50) and in patients with chronic periodontitis (N=102) in comparison to healthy controls (no periodontitis, no arthritis N=102). MATERIAL AND METHODS: HLA-class I and II markers were determined using microlymphocytotoxicity test and polymerase chain reaction with sequence specific primers. Statistical analyses were carried out by chi(2)-test and Yates' correction. If n<5 Fisher's exact test was performed. In the arthritis group the influence of HLA on attachment loss was determined by using backwards logistic regression considering age, gender, smoking, plaque level, and the duration of the disease. RESULTS: In comparison with the controls HLA-DRB3(*) occurred more frequently in both females suffering from juvenile idiopathic arthritis (74.58%versus 54.54%, p=0.024) and females suffering from chronic periodontitis (73.02%versus 54.54%, p=0.035). Furthermore, among patients with juvenile idiopathic arthritis an increased odds ratio (OR) for attachment loss was found in subjects who expressed HLA-A(*)01 (OR=4.6, p=0.014) or HLA-A(*)01:DRB3(*) (OR=4.3, p=0.031). CONCLUSION: HLA-DRB3(*) could be a common putative risk indicator for juvenile idiopathic arthritis and chronic periodontitis among females.

Distinct clinical differences between HLA-Cw*0602 positive and negative psoriasis patients--an analysis of 1019 HLA-C- and HLA-B-typed patients.

A major susceptibility gene for psoriasis is located in the major histocompatibility complex class I region on chromosome 6 very close to the HLA-Cw6 gene. We collected a cohort of 1,019 patients with chronic plaque psoriasis. The patients were typed for HLA-C and HLA-B. A total of 654 (64.2%) were HLA-Cw*0602 positive but 365 (35.8%) carried other HLA-C alleles. We confirmed that HLA-Cw*0602 positive patients have younger age of onset (17.5 vs 24.3 years, P<10(-10)), higher incidence of guttate and the eruptive type of psoriasis (P<0.0001), more frequent exacerbations with throat infections (P=0.01), higher incidence of the Koebner's phenomenon (P=0.01), and more extensive disease (P=0.03). A striking new finding was a diverging pattern of disease severity in HLA-Cw*0602 positive and negative patients depending on the age of onset of the disease (P=0.0006). HLA-Cw*0602 positive women also had more frequent remissions during pregnancy (P<0.0001). All types of nail changes were, however, more common in the Cw*0602 negative patients (P=0.003) and they more often had multiple types of nail lesions (P<0.0001). The three ancestral haplotypes of Cw*0602 all conferred an increase in odds ratio but showed no difference in any of the clinical features studied. Our findings indicate that the genetic factor on chromosome 6 has a strong influence on the phenotype of the disease, and underline that differences in clinical features of psoriasis may be to a large extent genetically determined.

Analysis of T cell receptor alpha-chain variable region (Valpha) usage and CDR3alpha of T cells infiltrated into lesions of psoriasis patients.

Psoriasis is a common inflammatory skin disease and is considered as T cell-mediated immune response. In this study, we analyzed T cell receptor alpha-chain variable region (TCR Valpha) usage in the lesions of psoriasis patients using 5'-RACE. As the results, Valpha1, -2, -7, -8, -10, -11, -12, and -23 were commonly detected in psoriatic lesions and comparison of expressions of these Valpha types between psoriasis patients and healthy individuals showed that Valpha1, -7, -11, and -12 were highly increased in psoriasis patients than in healthy individuals. Compared with atopy dermatitis patients, the expressions of Valpha1 and Valpha7 were increased in psoriasis patients. Then, to identify CDR3alpha of T cells infiltrated in psoriatic lesions, we examined which type of J gene segment was rearranged with Valpha1 or Valpha7, which the expressions was specifically increased in psoriatic lesions. The result showed that the V-J rearrangements between the examined patients were not equivalent and their frequencies were diverse, however, several common rearrangements such as Valpha1-Jalpha13, -23, -27, or -34 and Valpha7-Jalpha12, -33 were detected. The results in this study might provide the clue to define the characteristics of T cells associated with the pathogenesis of psoriasis.

[Genetics in patients with psoriatic arthritis]. / Arthritis psoriaticaában szenvedo betegek genetikai vizsgálata.

OBJECTIVES: HLA antigens were studied in 100 Hungarian patients suffered from psoriatic arthritis. Genetic markers for the development of different clinical pattern of the disease and skin disorder were identified. METHODS: Determination of class I and class II antigens was performed by using microlymphocytotoxicity assay. RESULTS: The frequency of HLA-Cw6, HLA-B16 (and its split B-39) and HLA-B27 antigens were significantly higher in psoriatic arthritis patients than in the Hungarian general population. No connection was found between HLA-DR4, DR7, B17 antigens and psoriatic arthritis. The patients were classified according to the subgroups proposed by Gladman. The comparisons between the clinical subgroups revealed a significant association of HLA-B27 with spondylitis (Gladman 4, 5, 6, 7). There was no association between HLA DR4 and polyarticular pattern of the disease (Gladman 3, 7). Psoriasis seemed to be significantly associated only with HLA-Cw6. There was a higher frequency of HLA-B38 in psoriatic arthritis patients with erythroderma.

Classic Kaposi's sarcoma in Sardinia: HLA positive and negative associations.

BACKGROUND: The incidence of classic Kaposi's sarcoma (CKS) in northern Sardinia is one of the highest in the world. METHODS: Sixty-two patients with CKS were typed for class I and class II antigens. All patients had been born and were living in northern Sardinia. RESULTS: In the Sardinian patients, we observed a positive CKS association with Cw7, DRB1*1104, DRB1*1302, DQA1*0302, and DQB1*0604, and a negative CKS association with A30, B58, Cw5, DRB1*1601, and DQB1*0502. CONCLUSIONS: The strong positive CKS association with DRB1*1104 and DQB1*0604 and negative association with B58 are particularly significant and further support the notion of a genetic predisposition to CKS.