This study was conducted to determine whether CD4 T cell responses to citrullinated fibrinogen occur in patients with rheumatoid arthritis (RA), especially in HLA-DR4-positive subjects. Whole peripheral blood mononuclear cells (PBMCs) of RA patients and control subjects were stimulated with citrullinated fibrinogen peptides, and T-cell production of proliferation and proinflammatory cytokines, such as interferon-gamma(IFN-gamma) and interleukin-17A (IL-17A), were measured. In addition, CD4 T cells from RA patients were stimulated with the citrullinated fibrinogen peptide, Fib-alpha R84Cit, identified as a DRB1*0401-restricted T cell epitope in HLA-DR4 transgenic mice, and the degree of T cell activation was examined similarly. No proliferative responses to the citrullinated fibrinogen peptides were observed in whole PBMCs or CD4 T cells from RA patients. Furthermore, no increased production of IFN-gamma or IL-17A was found in whole PBMCs or CD4 T cells stimulated with the citrullinated fibrinogen peptides, although these cells responded to recall antigen, a mixture of tetanus toxoid, purified protein derivative (PPD) from Mycobacterium tuberculosis, and Candida albicans. The results of this study indicate that anti-citrulline immunity in RA patients may be mediated by fibrinogen because there is no evidence of CD4 T cell-mediated immune responses to citrullinated fibrinogen peptides.
Animals ; Arthritis, Rheumatoid ; Candida albicans ; Cytokines ; Epitopes, T-Lymphocyte ; Fibrinogen ; HLA-DR4 Antigen ; Humans ; Interleukin-17 ; Mice ; Mice, Transgenic ; Mycobacterium tuberculosis ; Peptides ; T-Lymphocytes ; Tetanus Toxoid

A 30-year-old female patient with coexisting ankylosing spondylitis and rheumatoid arthritis was diagnosed and treated. The human leukocyte antigen (HLA)-B27 is a predisposing factor of ankylosing spondylitis and HLA-DR4 is a predisposing factor of rheumatoid arthritis. This patient was HLA-B27 and HLA-DR4 positive, and ankylosing spondylitis manifested before rheumatoid arthritis. After disease modifying anti-rheumatic drugs successfully arrested ankylosing spondylitis activity the patient conceived and delivered a healthy baby. One year later, she developed peripheral polyarthritis and was diagnosed with rheumatoid arthritis. We hypothesized that pregnancy may be one of the environmental factors that can activate rheumatoid arthritis, and that disease modifying anti-rheumatic drugs play an important role in keeping the disease under control.
Adult ; Arthritis, Rheumatoid ; diagnosis ; metabolism ; Female ; HLA-B27 Antigen ; metabolism ; HLA-DR4 Antigen ; metabolism ; Humans ; Spondylitis, Ankylosing ; diagnosis ; metabolism

OBJECTIVETo explore the association of the expressions of human leukocyte antigen (HLA)-DR4, peptidyl arginine deiminase type4(PAD4), and signal transducer and activator of transcription 4 (STAT4) in the peripheral blood with the disease activity in patients with rheumatoid arthritis (RA).

METHODSTwenty-four RA patients in active stage (DAS28 score>or=2.6) and 14 RA patients in remission stage (DAS28 score<2.6) were enrolled in this study, with 12 healthy volunteers as the control. The QuantiGene Plex method was used to measure the expression level of HLA-DR4, PAD4, and STAT4 mRNA, and the relationship between the expressions of these genes and the DAS28 score, levels of anti-cyclic citrullinated peptide antibody (anti-CCP antibody) and rheumatoid factor (RF) was analyzed.

RESULTSThe expressions of HLA-DR4, PAD4, and STAT4 were significantly higher in RA patients than in the healthy controls (P<0.05). The level of HLA-DR4 mRNA in the two RA groups showed no significant difference, but was significantly higher than that in the healthy controls. HLA-DR4 expression was not found to correlated to DAS28 score, anti-CCP antibody level or RF in the RA patients. The expressions of PAD4 and STAT4 were significantly different between the two RA groups (P<0.05). In the RA patients, PAD4 mRNA expression was positively correlated to DAS28 and anti-CCP antibody level (P<0.05), and STAT4 expression showed positive correlations to DAS28 and RF levels (P<0.05).

CONCLUSIONHLA-DR4, PAD4 and STAT4 are overexpressed in RA patients and may be involved in the pathogenesis of RA. The expressions of PAD4 and STAT4, but not HLA-DR4, are closely related to the disease activity of RA. Detection of peripheral blood PAD4 and STAT4 expressions can be helpful for evaluating the disease activity of RA.

Adult ; Arthritis, Rheumatoid ; blood ; Female ; HLA-DR4 Antigen ; blood ; genetics ; metabolism ; Humans ; Hydrolases ; blood ; genetics ; metabolism ; Male ; Middle Aged ; Protein-Arginine Deiminases ; RNA, Messenger ; genetics ; metabolism ; STAT4 Transcription Factor ; blood ; genetics ; metabolism

BACKGROUND/AIMS: Palindromic rheumatism (PR) is an episodic arthropathy that may precede typical rheumatoid arthritis (RA). The objective of this study was to determine whether anti-cyclic citrullinated peptide (anti-CCP) antibodies in patients with PR contribute to the progression to RA. METHODS: The study group included 115 patients who were initially diagnosed with PR. Baseline serum samples were stored and analyzed for the presence of anti-CCP antibodies, APF, and RF or for anti-CCP antibodies and HLA-DR4. A multiple logistic regression analysis was used to identify predictive factors for progression to RA. RESULTS: The anti-CCP antibodies APF and RF were found in 33.3%, 28.9%, and 35.7% of the 115 patients with PR, and 36 (31.3%) of these patients eventually progressed to RA. Comparing the risk factors for patients who progressed to RA (31.3%) and those who did not (68.7%), only the presence of anti-CCP antibodies was found to affect progression to RA (95% CI for OR, 0.0001-0.114; p<0.001). HLA-DR4-positivity was noted in 40% of the patients with PR, although it did not affect progression to RA and was not significantly associated with the presence of anti-CCP antibodies. CONCLUSIONS: Anti-CCP antibodies are found more frequently in patients with PR who eventually progress to RA. Therefore, anti-CCP antibody testing of patients with PR may facilitate prediction of progression to RA.
Antibodies ; Arthritis, Rheumatoid ; HLA-DR4 Antigen ; Humans ; Logistic Models ; Rheumatic Diseases ; Risk Factors

OBJECTIVETo study the effect of Yangqixue Qufengshi Recipe (YQXQFS) on rheumatoid arthritis (RA) model mice under different genetic backgrounds.

METHODSCollagen Induced Arthritis (CIA) were established on HLA-DR4 transgenic (TG) mice and non-transgenic (NTG) mice, which partly were raised with YQXQFS, and the onset day of CIA, the level of type II collagen (CII)-reactive antibodies and the pathological scores of CIA were assessed.

RESULTSUnder HLA-DR4 TG background (compared with NTG mice), the earlier onset day of CIA (11.22 +/- 3.35 days vs 16.56 +/- 4.75 days, P < 0.05) and higher level of CII-reactive antibodies (0.2274 +/- 0.1390 microg/ml vs 0.1101 +/- 0.0560 microg/ml, P < 0.05) were observed, but the pathological scores of CIA remained unchanged. YQXQFS could not influence the onset day of CIA and the level of CII-reactive antibodies, but had a certain effect on the total pathological scores (6.56 +/- 3.43 scores vs 11.11 +/- 5.64 scores) and bone erosion (0.22 +/- 0.44 scores vs 1.67 +/- 1.50 scores) of CIA on NTG mice (P < 0.05), NTG YQXQFS group compared with NTG experimental group.

CONCLUSIONYQXQFS had a certain effect on RA model, but had no significant effect on HLA-DR4 related CIA.

Animals ; Antibodies ; blood ; Antirheumatic Agents ; therapeutic use ; Arthritis, Experimental ; drug therapy ; Arthritis, Rheumatoid ; drug therapy ; immunology ; pathology ; Collagen Type II ; immunology ; Drugs, Chinese Herbal ; therapeutic use ; HLA-DR4 Antigen ; genetics ; Mice ; Mice, Inbred Strains ; Mice, Knockout

Human Leukocyte Antigen (HLA) typing of large groups of patients with various autoimmune diseases has demonstrated that some HLA alleles occur at higher frequencies in specific diseases than in the general population. Chronic urticaria has been shown to have an autoimmune basis by a previous study which found an association between chronic urticaria and specific HLA groups. We investigated the HLA subtypes of Turkish chronic urticaria patients. For this purpose 42 Turkish patients with chronic urticaria and 115 healthy controls were typed for HLA-DR and DQ by PCR-SSP (Polymerase Chain Reaction Sequence Specific Primers) low resolution DNA technique. We found an increased frequency of DR4 (42.9%, p=0.01) in chronic urticaria patients in comparison with that in healthy controls. This study supports the hypothesis that HLA alleles may be involved in the pathogenesis of chronic urticaria and that they appear to be directly involved in the initiation of the immune response.
Chronic Disease ; HLA-DQ Antigens/genetics ; HLA-DR Antigens/genetics ; HLA-DR4 Antigen/genetics ; Histocompatibility Antigens Class II/*genetics ; *Histocompatibility Testing ; Human ; Urticaria/*genetics/*immunology

PURPOSE: Vogt-Koyanagi-Harada syndrome is more common in adults than in children. We report a atypical case of Vogt-Koyanagi-Harada syndrome like white dot syndromes in a 7-year-old child. METHODS: A 7-year-old child visited with complaints of decreased binocular visual acuity. Under ophthalmologic examination, anterior uveitis and optic neuropathy were found. But there was no other retinal lesion. After high-dose intravenous corticosteroids pulse therapy, yellow pigment lesions like white dot syndromes developed in peripheral retina and enlarged without serous retinal detachment. RESULTS: In 5 months after high-dose intravenous corticosteroids pulse therapy, anterior inflammation was decreased and visual acuity was 0.8 in both eyes. But depigmented retinal lesions were increased and sunset glow occurred. Alopecia and poliosis of hair were found. Human leukocyte antigen typings revealed HLA-DR4 antigen.
Adrenal Cortex Hormones ; Adult ; Alopecia ; Child* ; Hair ; HLA-DR4 Antigen ; Humans ; Inflammation ; Leukocytes ; Male* ; Optic Nerve Diseases ; Retina ; Retinal Detachment ; Retinaldehyde ; Telescopes ; Uveitis, Anterior ; Uveomeningoencephalitic Syndrome* ; Visual Acuity

OBJECTIVETo investigate the relationship between tumor necrosis factor A-308 gene polymorphism and susceptibility of severe periodontitis in adults.

METHODSBuccal swabs from 65 adult patients with severe periodontitis and 96 periodontal healthy adult controls were obtained. DNA was extracted from each sample using Chelex-100 method, then PCR-RFLP was performed to determine the TNFA-308 genotype. Data were analyzed by statistics software.

RESULTSA significant difference of genotype distribution was found between the patients and controls. The percentage of 1/1 type of the patients was much higher (P < 0.001). Risk Analysis showed odds ratio for allele 1 was 4.64.

CONCLUSIONThis study suggested that TNFA-308 allele 1 maybe a marker of susceptibility to severe periodontitis.

Adult ; Genetic Predisposition to Disease ; HLA-DR4 Antigen ; genetics ; Humans ; Periodontitis ; genetics ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Tumor Necrosis Factor-alpha ; genetics

OBJECTIVETo analyze the association between alleles of HLA-DRB1 and type I autoimmune hepatitis (AIH) in patients from Shanghai, China.

METHODSIn 32 Chinese patients with type I AIH and 48 healthy controls in Shanghai area, polymerase chain reaction amplification with sequence-specific primers (PCR-SSP) was performed to examine the association of the alleles of HLA-DRB1 and its subtypes with type I AIH.

RESULTSHLA-DRB1 typing by PCR-SSP showed that DR4 had a significantly increased frequency among patients with AIH versus healthy control (46.9% versus 20.8%; relative risk=3.35, chi(2)=5.99, P=0.014). No other alleles differed significantly between the two groups. In subtypes of DRB1*04, there was a trend for an increase in gene frequency of DRB1*0405 increased in patients with type I AIH versus healthy controls (21.9% vs 6.3%, chi(2)=4.23, P=0.04, but Pc=0.08). The frequency of arginine at position HLA-DR beta 71 of third hypervariable region significantly increased among patients with AIH versus healthy control (46.9% versus 18.8%, chi(2)=7.14, P=0.008).

CONCLUSIONSType I AIH in Chinese patients of Shanghai area is associated with HLA-DR4 and arginine at position DR beta 71 of third hypervariable region

Alleles ; Asian Continental Ancestry Group ; China ; DNA Primers ; Gene Frequency ; HLA-DR4 Antigen ; HLA-DRB1 Chains ; genetics ; Hepatitis, Autoimmune ; genetics ; Humans ; Polymerase Chain Reaction

OBJECTIVE: A genetic predisposition is widely accepted in schizophrenia. This study was intended to find any association of HLA-DRB1 alleles with Korean schizophrenics and thereby compare the results of other ethnic groups. METHODS: The subjects were 70 unrelated Korean patients. Low and high resolution typing of HLA-DRB1 alleles were performed. The comparison groups were 2,000 unrelated healthy Koreans for low resolution HLA-DR and 229 unrelated healthy Koreans for HLA-DRB1 alleles. RESULTS: Gene frequencies of HLA-DR11(patients 9.0%, healthy control 3.8%, p=0.005) and HLA-DRB1*1101(patients 9.0%, healthy control 1.8%, p< .001) were significantly higher in Korean schizophrenics. CONCLUSIONS: The frequency of HLA-DR11 (HLA-DRB1*1101) is significantly higher in Korean schizophrenics than in healthy Koreans. HLA-DR4 and HLA-DR1, which were known to be associated with Caucasian and Japanese schizophrenics, respectively, did not show statistical association with Korean schizophrenics. This association need to be reassured through further studies with families or association study with larger numbers of subjects.
Alleles* ; Asian Continental Ancestry Group ; Ethnic Groups ; Gene Frequency ; Genetic Predisposition to Disease ; HLA-DR Antigens ; HLA-DR1 Antigen ; HLA-DR4 Antigen ; HLA-DRB1 Chains* ; Humans ; Schizophrenia