Interleukin-1 receptor antagonist gene in multiple sclerosis.
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Alleles↗
Biomedical subjects
G Semana
Publications and source records attributed to G Semana.
Tumor necrosis factor a microsatellite polymorphism in rheumatoid arthritis: comment on the article by Hajeer et al.
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Arthritis, Rheumatoid↗
Interaction between certain major histocompatibility complex class II and T-cell receptor V beta alleles promotes the antibody production to extractable nuclear antigen-related peptides.
Our objective was to study the interaction between major histocompatibility complex (MHC) class II and T-cell receptor (TCR) alleles in the recognition of extractable nuclear antigen-derived peptides in 32 patients with systemic lupus erythematosus and 173 of their family members. MHC genes were analyzed using sequence specific oligonucleotides, and TCR beta-chain gene polymorphism using restriction fragment-length polymorphism. One dominant peptide (as defined by enzyme-linked immunosorbent assay autoantibody reactivity) was identified in each antigen studied: peptide 1-20 in Sm-D, peptide 35-58 in U1-RNP-A, and peptide 304-324 in the Ro/SSA 60 Kd protein. None of the MHC class II and TCR beta haplotypes was directly associated with any of the autoantibodies. Twenty-six subjects had antibodies to the peptide Sm-D1-20; nine of them were DRB1*0101/DQB1*0501. Among subjects with this haplotype, the number of responders was higher (p < 0.028, p corrected, pc = 0.336) in those with the 2-25-9 TCR beta haplotype than in the remainder. Conversely, the number of DRB1*04/DQB1*0302 responders was lower (p < 0.030, pc = 0.360) among subjects with the 23-20-9 TCR beta haplotype than in those without. The odds ratios (OR) were 4.23 and 0.21, respectively. Of the 54 subjects positive for anti-U1-RNP-A 35-38, 13 were DRB1*0101/DQB1*0501 and eight DRB1*04/DQB1*0302. The percentage of responders was higher (p < 0.041, pc = 0.492, OR = 3.48) in the former group of subjects with the 2-25-9 TCR beta haplotype, and lower (p < 0.02, pc = 0.024, OR = 0.09) in the latter with the 23-20-9 TCR beta haplotype. Three of the 12 anti Ro/SSA 60Kd 304-324-positive subjects were DRB1*0101/DQB1*0501. All had the 2-25-9 TCR beta haplotype (p < 0.046, pc = 0.552, OR = 6.29) and none the 23-20-9 (p < 0.031, pc = 0.372, OR = 0.10). The same combinations of genes were associated with high/low response toward the three peptides. These data provide evidence for an interplay of the MHC class II and TCR beta alleles in the control of specific autoantibody response to well-defined nuclear Ag peptides.
Adolescent↗
Human monocyte-derived macrophages and dendritic cells are comparably effective in vitro in presenting HLA class I-restricted exogenous peptides.
Recent experimental data have shown that mice could be immunized efficiently, in particular against cancer, by the injection of antigen-loaded dendritic cells (DC) or macrophages (MPH). In the present work, these two antigen-presenting cells (APC) were prepared in humans from circulating mononuclear cells (MNC). MPH were obtained from MNC that were cultured in hydrophobic plastic bags and purified by elutriation. DC were from the culture of adherent elutriation-purified monocytes in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). The two APC were prepared in parallel from the same donors and their phenotype and antigen-presenting capacity were compared. DC differed from MPH by a higher expression of HLA-DR and CD23 and a lower expression of CD14, CD64 and of adhesion molecules. DC and MPH were comparably effective in (a) enhancing the mitotic response of autologous lymphocytes to immobilized anti-CD3 (accessory function); (b) presenting melanoma peptides to specific cytotoxic T lymphocyte (CTL) clones; and (c) stimulating the generation of CTL directed against a myxovirus influenza peptide. However, DC were more effective than MPH in inducing the mitotic response of allogeneic peripheral blood leucocytes (PBL), possibly because of their higher expression of HLA class II molecules. In conclusion, DC and MPH prepared from blood MNC did not differ substantially in their ability to activate HLA class I-restricted T-cell responses by exogenous peptide presentation.
Antigen Presentation↗
TAP gene transporter polymorphism in inflammatory bowel diseases.
BACKGROUND: Many studies suggest the implication of genetic factors in inflammatory bowel diseases. Despite some associations with HLA genes, the lack of definite data may be due to ethnic variations, clinical heterogeneity, or the involvement of additional susceptibility genes beside or within the major histocompatibility complex (MHC), such as TAP genes. The aim of this study was to analyze in patients with ulcerative colitis (UC) or Crohn's disease (CD) the polymorphism of TAP genes that encode the proteins necessary for the transfer of antigenic peptides through the endoplasmic reticulum membrane. METHODS: One hundred and one UC and 148 CD patients were compared with 173 unrelated healthy controls. Dimorphisms within the TAP1 and TAP2 alleles were analyzed by sequence-specific oligonucleotide typing. RESULTS: No difference was found between patient groups and controls. However, when CD patients were classified on the basis of their responsiveness to steroid therapy, a significant decrease of TAP2 AA (*0101/*0101) genotype was found in CD patients who did not respond to steroid therapy (22.9% versus 43.7% in steroid responder group; Pc < 0.05; odds ratio = 2.6; 95% confidence limits (CL) = 1.2-5.9). These data appear independent of the distribution of HLA DRB1*01 or DRB1*03 alleles despite a significant linkage disequilibrium between these alleles and TAP2A. CONCLUSIONS: This result suggests, despite the absence of arguments favoring a genetic susceptibility to CD, that the TAP2 gene or other genes located on chromosome 6 may be involved in the genetic heterogeneity of CD.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Significance of interleukin-1beta and interleukin-1 receptor antagonist genetic polymorphism in inflammatory bowel diseases.
OBJECTIVE: Genetic susceptibility to inflammatory bowel disease is well recognized. There is also increasing evidence for the activation of the mucosal immune system and the production of inflammatory cytokines, i.e., interleukin (IL)-1ra and IL-1beta in the inflammatory bowel disease. The aim of this study was to analyze the IL-1beta and IL-1ra gene polymorphism and linkage disequilibrium coefficient between the different alleles of these genes in patients with Crohn's disease (CD) or ulcerative colitis (UC), according to the severity of the disease. METHODS: Two hundred twenty-eight inflammatory bowel disease patients (87 UC and 141 CD) were included in this study and compared with 113 unrelated controls. The IL-1beta and IL-1ra gene polymorphism was studied after specific amplification of variable regions by PCR. A penta-allelic polymorphism, corresponding to a VNTR region located in intron 2 of the IL-1ra gene, was analyzed, whereas bi-allelic RFLPs displayed by two restriction enzymes (TaqI and AvaI) at position -511 of the IL-1beta gene were analyzed. RESULTS: There was no significant difference of genotype distribution between controls and CD or UC patients. However, surgically treated UC patients were characterized by a higher frequency of genotype IL-1ra 1-2 (39 vs 16%, pc < 0.01) compared with nonoperated UC patients. Moreover, nonoperated UC patients displayed a lower frequency of IL-1ra allele 2 than surgically treated UC patients (14 vs 34%, pc < 0.002) or controls (14 vs 30%, pc < 0.005). Furthermore, simultaneous analysis of the IL-1beta and IL-1ra genes that are located in the same region of chromosome 2 revealed that CD patients carrying the IL-1beta allele 2 were more often noncarriers of IL-1ra allele 2 (p < 0.005). Moreover, UC and CD patients were, characterized by a lower frequency of the association of IL-1ra allele 2 and IL-1beta allele 2 compared with controls (8.3 vs 20.3% and 10.6 vs 20.3%, p < 0.03). CONCLUSIONS: IL-1ra and IL-1beta gene polymorphism analysis from a clinical standpoint might help in defining UC prognosis. However, functional studies at both the circulating and mucosal level with stratification on allele associations, especially IL-1ra allele 2-IL-1beta allele 2 subgroups must be realized before therapeutic implications.
Adult↗
Role of HLA-DR-DR and DR-DQ associations in the expression of extraarticular manifestations and rheumatoid factor in rheumatoid arthritis.
OBJECTIVE: To investigate the role of HLA-DRB1 genotypes and HLA-DRB1*0401-DQB1*03 haplotypes in the expression of extraarticular manifestations and rheumatoid factor (RF) in rheumatoid arthritis (RA). METHODS: 189 patients with RA were classified according to the presence of vasculitis and seropositivity for RF. IgM RF were determined by at least 2 of the following methods: standard latex agglutination, the Waaler-Rose test, and nephelometry. HLA genotyping was performed by reverse dot blot hybridization for DRB1 alleles and the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for DQB1 alleles. RESULTS: The QKRAA susceptibility sequence, which characterizes the HLA-DRB1*0401 allele, was observed in 71.5% of the 21 patients with vasculitis and 57.6% of the 158 RF positive patients. The influence of a 2nd allele within the major histocompatibility complex was observed but the allele differed according to the clinical features examined. Higher risk for vasculitis was observed in patients who carried 2 DRB1 susceptibility alleles, one characterized by the QKRAA sequence and the other by the QRRAA sequence (OR = 3). Conversely, the higher risk for IgM RF positivity was observed in patients who carried the QKRAA sequence of the DRB1 alleles with the DQB1*0301 alleles of the DQ region (OR = 4.7). CONCLUSION: Our data suggest that a distinct immunogenetic association is involved in the extraarticular manifestations of RA and in the expression of RF.
Adult↗
[Polymorphism of the microsatellites and tumor necrosis factor genes in chronic inflammatory bowel diseases].
OBJECTIVES: Multiplex family studies have excluded chromosome 6 as a candidate gene of susceptibility to inflammatory bowel disease. However, one recent study suggested that a gene involved in the pathogenesis of Crohn's disease is located on chromosome 6 confering to a microsatellite allelic combination (a2, b1, c2, d4, e1) a strong genetic risk factor in Crohn's disease. The aim of our study was to determine simultaneously the polymorphisms of the TNF microsatellites and of the genes coding for TNF synthesis in patients with inflammatory bowel disease. PATIENTS AND METHODS: Sixty patients with ulcerative colitis, 100 patients with Crohn's disease were compared to 64 healthy ethnically matched controls. Five TNF microsatellite loci (a, b, c, d, e) were typed using polymerase chain reaction PCR, and two dimorphisms of TNF alpha and TNF beta (intron 1) were studied by restriction fragment length polymorphism (RFLP). RESULTS: Allelic frequencies of TNF microsatellites and of TNF alpha and beta genes were similar in Crohn's disease, ulcerative colitis and controls. Five loci microsatellite haplotypes, especially a2 b1 c2 d4 e1 allelic combination, were not more frequent in Crohn's disease (25%) compared to ulcerative colitis (27%) or controls (20%). Subgroups stratification according to clinical characteristics did not modify haplotype frequencies. Analysis of our data taking simultaneously into account the MHC alleles (DRB*01 or DRB1*04) did not modify our data; however, it suggested that extended haplotype on short arm of chromosome 6 differed between patients and controls. Linkage disequilibrium (delta = -360.10(-4); P < 0.01) between a2, b1, c2, d4, e1 allelic combination and DRB1*04 allele was observed only in Crohn's disease. CONCLUSION: Percentages of patients with Crohn's disease or ulcerative colitis carrying TNF microsatellite or TNF alpha and beta gene haplotypes were similar to those of healthy controls. These data argue against involvement of the TNF locus without exclusion of short arm of chromosome 6 implication in Crohn's disease pathogenesis.
Adult↗
Selection of T cells reactive against autologous B lymphoblastoid cells during chronic rheumatoid arthritis.
The repertoire and Ag specificity of T cells infiltrating inflamed joints from a chronic rheumatoid arthritis (RA) patient were studied in detail. Repertoire analysis demonstrated a reduced clonality of joint-infiltrating lymphocytes (JIL) as compared with patient's PBL, which was presumably due to an intra-articular expansion of T cell clones with recurrent TCR features. Strikingly, a large fraction of these JIL T cell clones, which were predominantly CD8+, proliferated in vitro when exposed to autologous B lymphoblastoid cells (BLC), unlike randomly chosen PBL clones derived from the same patient. This proliferative response was HLA-restricted, which confirmed a classical TCR-mediated recognition of BLC and was not observed against autologous PHA blasts, suggesting recognition of either EBV or B cell-specific Ags. Finally, a preliminary analysis of synovial lymphocytes derived from another chronic RA patient demonstrated a similar enrichment for T cells reactive against autologous BLC within JILs as compared with patient's PBLs. Taken together, these results, which suggest frequent expansions of autologous BLC-reactive T cells within inflamed joints of chronic RA patients, provide a basis for future studies evaluating the fine specificity and pathogenicity of these lymphocytes.
Adult↗
T cell response to Epstein-Barr virus transactivators in chronic rheumatoid arthritis.
Rheumatoid arthritis is a multistep disorder associated with autoimmune features of yet unknown etiology. Implication of viruses such as Epstein-Barr virus (EBV) in rheumatoid arthritis pathogenesis has been suspected on the basis of several indirect observations, but thus far, a direct link between EBV and rheumatoid arthritis has not been provided. Here we show that a large fraction of T cells infiltrating affected joints from a patient with chronic rheumatoid arthritis recognizes two EBV transactivators (BZLF1 and BMLF1) in a major histocompatibility complex-restricted fashion. Responses to these EBV antigens by synovial lymphocytes from several other chronic rheumatoid arthritis patients were readily detectable. Thus these results suggest a direct contribution of EBV to chronic rheumatoid arthritis pathogenesis. They also demonstrate for the first time the occurrence of T cell responses against EBV transactivating factors, which might be central in the control of virus reactivation.
Animals↗
Interplay of four idiotypes and interaction with autoantibodies in lupus patients, their relatives and their spouses.
Our aim was to investigate links between systemic lupus erythematosus (SLE)-associated autoantibodies, idiotypes (Id) and genetic predisposition to their development. We studied four public Ids (16/6, WRI 176 beta, RT72 and RT84), identified the Km and Gm phenotypes and sought six selected autoantibodies in 32 SLE patients, 174 of their relatives and 15 spouses. Though anti-double-stranded DNA antibody was uncommon in the relatives (9%), the range of antinuclear reactivities was as broad in the relatives as in the probands. Antibodies to the synthetic peptide U1-RNP-A 35-38 were found in 56% of the patients, 28% of their relatives and 20% of the spouses, whereas antibodies to the Golgi apparatus was present in 7% of the patients, 26% of their relatives and 33% of the spouses. However, most of these family members were unaffected. RT84 Id was positively associated with antibodies to Sm-D peptide 1-20 and to Ro/SSA 60 kD peptide 304-324, but negatively associated with anti-dsDNA activity. The median of age was significantly lower in the RT84 Id-positive than in the RT84 Id-negative individuals. These data suggest that genetic as well as environmental factors are involved in the aetiology of SLE. In addition, RT84-carrying immunoglobulins (Ab2) might be directed to one of many cross-reactive Ids of dsDNA-binding antibodies (Ab1), perhaps down-regulating their production.
Adolescent↗
Are HLA-DR or TAP genes genetic markers of severity in ulcerative colitis?
The pathogeny of ulcerative colitis (UC) is not yet elucidated, but some arguments suggest the implication of genetic factors. Among the candidate genes, those encoding for HLA class II genotypes have been extensively studied in UC; however, discordant data may be imputable to heterogeneity, characterized by immunological markers such as atypical ANCA (p-ANCA), or to inclusion of more or less intractable UC. The aim of our study is to evaluate the interest of HLA class II and TAP genetic markers to identify different clinical forms of UC, according to p-ANCA status. Unrelated patients with a history of UC (n = 91) and healthy control subjects with no personal or family history of inflammatory bowel diseases (IBD) (n = 200) were included. HLA-DRB1*03 was less frequent in UC patients than in healthy controls (8% vs 28%, PC < 0.03). No association was found with any TAP genotypes. Moreover, there was no association with the HLA-DR2 specificity, either in the entire group of UC patients (38% vs 28%) or in the p-ANCA-positive subgroup of patients (30%). The most consistent finding in the present study is that some genetic markers may characterize intractability in UC patients. HLA-DR2 was associated with poor prognosis, regardless of p-ANCA status. In HLA-DR2 and non-HLA-DR2 groups, colectomy was done in 55% and 27% of patients, respectively, (PC < 0.05). Furthermore, in non-HLA-DR2 patients, p-ANCA could be of interest to characterize those with more severe prognosis. Our results confirm the interest of genetic studies to define UC genetic susceptibility, taking into account intractability of the disease. They do not support the hypothesis that p-ANCA is a subclinical marker of genetic susceptibility to UC.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
The role of HLA-DR-DR and HLA-DR-DP interactions in genetic susceptibility to rheumatoid arthritis.
In order to analyze the relationships between the DR and DP loci in the genetic susceptibility to RA, HLA-DRB1 and -DPB1 polymorphism was studied in 155 RA patients compared to 150 controls, using a reverse dot-blot analysis. Our data were consistent with the involvement of the amino acid in position 71 of the third hypervariable region of the DR beta 1 chain in susceptibility to the disease. The higher risk for RA was observed in patients who carried the association of a lysine (K), characterizing the DRB1* 0401 susceptibility allele, with an arginine (R), observed in all the other DRB1* susceptibility alleles (21.9% vs 0.6%, p(c) < 10(-6), OR = 42) In the absence of arginine, the presence of lysine was still associated with the disease (33% vs 19%, p(c) < 0.03, OR = 2). In contrast, in the absence of lysine, the frequency of arginine in position 71 was similar in patients and controls (30% vs 26%, p = NS). On another hand, the analysis of the HLA-DPB1 locus showed that the DPB1 *0401 allele frequency was significantly increased in the RA patient group (n = 47) who expressed only arginine at the position 71 of the beta 1 chain (82% vs 56% in controls, p < 0.008), with role of HLA-DR--DR and -DR-DP interactions in the genetic susceptibility to RA.
Alleles↗
Genetic susceptibility and anti-human platelet antigen 5b alloimmunization role of HLA class II and TAP genes.
Platelet alloimmunization may result in post-transfusion purpura, and during pregnancy may cause neonatal alloimmune thrombocytopenia (NAIT), with a frequency estimated at 1.3 per 1000 live births. The risk of morbidity is significant: 20% of affected infants have neurologic sequelae and the death rate is about 10%. A better understanding of the immune response to platelet alloantigens would allow for a better definition, and thus better management of pregnant women at high risk. Limited data are available on the immune response against HPA-5b, the second most frequent antigen, after HPA-1a, implicated in NAIT. We studied HLA class II and TAP gene polymorphism in 50 women immunized against HPA-5 system antigens. Our results suggest a strong association of alloimmunization with a cluster of HLA DR molecules sharing a particular polymorphic amino acid sequence at position 69-70 (Glu-Asp encoded by GAA-GAC nucleotide sequence) of the DR beta 1 chain (RR = 2.95, RR = 5.70 when patients were homozygous for this sequence), and a negative association with the DRB1*0301 allele (2.1% vs. 28%; RR = 0.08). Furthermore, increased frequency of a TAP2 dimorphism at position 379 was observed in immunized women against the HPA-5 antigens (RR = 4.7).
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Genetic heterogeneity between type 1a and type 1b insulin-dependent diabetes mellitus: HLA class II and TAP gene analysis.
The aim of this study was to compare the genetic susceptibility linked to the HLA Class II region genes of the Major Histocompatibility Complex in isolated insulin-dependent diabetes mellitus (1a-IDDM) and insulin-dependent diabetes mellitus associated with another autoimmune endocrinopathy (1b-IDDM). HLA genes DRB1, DQA1 and DQB1 were studied at the genomic level, as well as genes TAP1 and TAP2. One hundred and seventy-nine 1a-IDDM diabetic patients were compared with 83 1b-IDDM patients. While it appeared that common genetic traits characterize diabetes regardless of the subtype (1a or 1b), certain features differentiate the two forms of IDDM. Extending the analysis of risk haplotypes DRB1*03 and DRB1*04 to TAP genes elicited a difference between 1a-IDDM and 1b-IDDM patients. Haplo-type DRB1*03 was thus characterized in 1a-IDDM patients by a lower frequency of alleles TAP1-B (13.5%) and TAP2-B (16.2%), not found in 1b-IDDM patients (33.3% for each allele). Likewise, haplotype DRB1*04 is characterized in 1b-IDDM patients by a lower frequency of alleles TAP1-C (4.0%) and TAP2-B (8.0%) than in 1a-IDDM patients (22.2% and 25.9%, respectively). In total, this study showed that extending the characterization of HLA Class II haplotypes to TAP genes discriminates between the forms of diabetes restricted to a specific pancreatic affection and those reflecting a wider autoimmune disorder affecting several organs.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Distribution of HLA-G alternative mRNAs including soluble forms in normal lymphocytes and in lymphoid cell-derived leukemia.
The non-classical HLA-G gene is the only class I antigen expressed in trophoblasts at the maternofetal interface. In placenta, the HLA-G gene produces several alternatively spliced isoforms encoding bound-membrane proteins (G1, G2, G3 and G4) lacking, respectively, exon 7; exons 7 and 3; exons 7, 3 and 4, and exons 7 and 4. In addition, two isoforms (G1s and G2s) containing an intron 4 sequence are able to encode soluble antigens. We have recently reported that the HLA-G gene is transcriptionally active in lymphocytes and is not transcribed in CD34+ cells, polynuclear cells or monocytes. To investigate the functional significance of the different isoforms in lymphocytes, we studied their distribution in normal T and B lymphocytes and in malignant lymphoid cells by using the RT-PCR technique followed by hybridization with exon-specific probes and sequencing assays. In transcriptionally active lymphocytes, the HLA-G primary transcript is the major form and is differentially spliced in B and T lymphocytes: (i) G1s is found in several samples of T and B cells whereas G2s is only transcribed in T lymphocytes, (ii) the G4 isoform is never detected in B lymphocytes. In addition, we have shown that HLA-G is inactive in some samples of lymphocytes. Our data suggest that HLA-G transcription is regulated at the initiation level and at the subsequent splicing. These two levels of regulation may be dysregulated in some cases of T-ALL and CLL. The potential functions of the HLA-G alternative forms in lymphocytes, such as peptide binding and modulation of the immune response, are discussed.
Alternative Splicing↗
Investigation of the association of major histocompatibility complex genes, including HLA class I, class II and TAP genes, with clinical forms of Crohn's disease.
The aim of this study was to determine immunogenetic markers of susceptibility in Crohn's disease (CD), taking the different features of the clinical course of the disease into account. HLA class I, HLA class II and TAP transporter gene polymorphisms were studied using DNA typing methods. Gene and antigen frequencies were analysed and compared in a group of 102 CD patients and 200 unrelated healthy controls from the same area. Analysis of the whole CD patient population revealed no definite association with either HLA or TAP gene alleles, with the exception of an association with DRB1*1302 (Pc < 0.05). However, when clinical subgroups of patients were considered, specific associations with some genetic markers were found. The most definitive results involved a genetic association in the group of patients who did not respond to glucocorticoid therapy. This group was characterized by a high frequency of HLA-DRB1*04 (P < 0.05). Conversely, a positive association with the TAP2-A allele was found in cortico-responder patients (Pc < 0.03). Furthermore, analysis of the distribution of HLA class II alleles in relation to the presence of extra-intestinal manifestations revealed an association with the DQB1*0501 or *0503 suballele of DQ5 (P < 0.05). Finally, patients with lesions in the small bowel were more frequently HLA DRB1*07 (P < 0.05). The present study supports the concept of clinical heterogeneity in Crohn's disease associated with a background of genetic heterogeneity.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Association of HLA class II genes with susceptibility to Crohn's disease.
BACKGROUND: Published studies on the association between HLA class II genes and inflammatory bowel disease are contradictory perhaps because of the limited size and ethnic heterogeneity of the populations studied. AIM: To compare the frequencies of HLA class II genes in a large number of French patients with Crohn's disease and in an ethnically matched control group. METHODS: 344 patients (196 F, 148 M, mean age 23.6 years) with Crohn's disease were molecularly genotyped for the HLA-DQB1 and DRB1 alleles. The results were compared with those for an ethnically matched control population of 488 white adults. RESULTS: There were two significant variations of alleles at the DQB1 locus: an increase in DQB1*0501 allele frequency (chi 2 = 10.6, corrected p value (pc) = 0.01, odds ratio (OR) = 1.61) and a decrease in DQB1*0602/0603 allele frequencies (chi 2 = 8.43, pc = 0.037, OR = 0.66). DRB1 analysis showed associations with three allelic variations: an increase in the frequencies of DRB1*01 (chi 2 = 12.86, pc = 0.003, OR = 1.75) and DRB1*07 alleles (chi 2 = 11.18, pc = 0.008, OR = 1.58) and a very significant decrease in that of the DRB1*03 allele (chi 2 = 19.7, pc = 9.10(-5), OR = 0.46). CONCLUSION: The alleles DRB1*01 and DRB1*07 are associated with susceptibility to Crohn's disease. The strong negative association between the DRB1*03 allele and Crohn's disease suggests that the HLA-DRB1*03 allele mediates 'resistance' to Crohn's disease.
Adolescent↗