Background: Systemic lupus erythematosus (SLE) is an autoimmune disease under genetic control. Growing evidences support the genetic predisposition of HLA-DRB1 gene polymorphisms to SLE, yet the results are not often reproducible. The purpose of this study was to assess the association of two polymorphisms of HLA-DRB1 gene (HLA-DR3 and HLA-DR15) with the risk of SLE via a comprehensive meta-analysis. Methods: This study complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Case-control studies on HLA-DRB1 and SLE were searched from PubMed, Elsevier Science, Springer Link, Medline, and Cochrane Library database as of June 2018. Analysis was based on the random-effects model using STATA software version 14.0. Results: A total of 23 studies were retained for analysis, including 5261 cases and 9838 controls. Overall analysis revealed that HLA-DR3 and HLA-DR15 polymorphisms were associated with the significant risk of SLE (odds ratio [OR]: 1.60, 95% confidence interval (CI): 1.316-1.934, P = 0.129 and OR: 1.68, 95% CI: 1.334-2.112, P = 0.001, respectively). Subgroup analyses demonstrated that for both HLA-DR3 and HLA-DR15 polymorphisms, ethnicity was a possible source of heterogeneity. Specifically, HLA-DR3 polymorphism was not associated with SLE in White populations (OR: 1.60, 95% CI: 1.320-1.960, P = 0.522) and HLA-DR15 polymorphism in East Asian populations (OR: 1.65, 95% CI: 1.248-2.173, P = 0.001). In addition, source of control was another possible source for both HLA-DR3 and HLA-DR15 polymorphisms, with observable significance for HLA-DR3 in only population-based studies (OR: 1.65, 95% CI: 1.370-1.990, P = 0.244) and for HLA-DR15 in both population-based and hospital-based studies (OR: 1.38, 95% CI: 1.078-1.760, P = 0.123 and OR: 2.08, 95% CI: 1.738-2.490, P = 0.881, respectively). Conclusions HLA-DRB1 gene may be a SLE-susceptibility gene, and it shows evident ethnic heterogeneity. Further prospective validations across multiple ethnical groups are warranted.
Case-Control Studies ; Gene Frequency ; genetics ; Genetic Predisposition to Disease ; genetics ; HLA-DR Serological Subtypes ; genetics ; HLA-DR3 Antigen ; genetics ; HLA-DRB1 Chains ; genetics ; Haplotypes ; genetics ; Humans ; Lupus Erythematosus, Systemic ; Odds Ratio ; Polymorphism, Genetic ; genetics

OBJECTIVETo explore the correlation between the HLA-DR13, basic core promoter (BCP), changes of T lymphocyte subset and clinical Chinese medical syndromes of chronic hepatitis B (CHB).

METHODSTotally 102 CHB patients were syndrome typed as Gan depression Pi deficiency syndrome (GDPDS), Pi-Shen yang deficiency syndrome (PSYDS), Gan-gallbladder dampness heat syndrome (GGDHS), Gan-Shen yin deficiency syndrome (GSYDS), and static blood blocking collaterals syndrome (SBBCS). Besides, 30 healthy subjects were recruited as the normal control group. The blood HBV-DNA level and HLA-DR13 gene were detected with real time fluorescent PCR. The expression of CD4+ and CD8+ in T lymphocytes was detected using flow cytometry. The mutation of serum A1762T/G1764A was detected using PCR sequencing. Hepatitis Be antigen (HBeAg) was detected with ELISA, and correlation between various Chinese medical syndrome types and objective indicators were analyzed.

RESULTSThere was no statistical difference in HBV-DNA quantitative results among various syndrome types (P > 0.05). HBeAg positive rate was higher in GDPDS than in other syndrome types (P < 0.05). It was sequenced as GDPDS > GSYDS > SBBCS > GGDHS > PSYDS. Compared with the normal control group, percentages of CD3+ and CD3+ CD4+ were lower in PSYDS (P < 0.05). The ratio of CD3+ CD4+/CD3+ CD8 was lower in GGDHS and PSYDS than in the normal control group (P < 0.05). There was no statistical difference in the CD3+ CD8+ percentage among various syndrome types (P > 0.05). The quantitation of HLA-DR13 gene was lower in GDPDS and GSYDS than in the normal control group (P < 0.05). The positive rate of BCP mutation was higher in GSYDS than in other syndrome types (P < 0.05).

CONCLUSIONCo-detection results of HLA-DR13 and BCP could be used as reference indices of Chinese medical syndrome typing of CHB.

HLA-DR Serological Subtypes ; genetics ; metabolism ; Hepatitis B, Chronic ; classification ; diagnosis ; genetics ; Humans ; Medicine, Chinese Traditional ; Promoter Regions, Genetic ; Syndrome ; T-Lymphocyte Subsets ; metabolism ; Yang Deficiency ; Yin Deficiency

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

Adolescent ; Adult ; Aged ; Alleles ; Child ; Female ; HLA-DR Serological Subtypes ; genetics ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; diagnosis ; genetics ; pathology ; Prognosis ; Young Adult

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

The objective of this study was to detect the expression frequency of HLA-DR15 in patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS), to investigate the relation of expression frequency with diseases and to analyze the relationship between immunoglobulin, T lymphocyte subsets and HLA-DR15. HLA-DR15 expression was detected by PCR-SSP; immunoglobulin was detected by immune turbidimetry; T cell subsets were detected by flow cytometry. The results showed that the expression rates of HLA-DR15 in AA and MDS as well as normal control groups were 78.6%, 63.2% and 24.6% respectively. The difference between AA, MDS and the normal control groups was statistically significant (p < 0.01). OR (odds ratios) values of AA and MDS groups were 11.262, 4.710 respectively. Compared with normal control group, expression rate of HLA-DR15 in hematologic malignancy group was not significantly different. The immunoglobulin level and abnormal T cell subsets in AA and MDS groups were statistically different between HLA-DR15 positive and negative groups (p > 0.05). It is concluded that the frequency of HLA-DR15 antigen in AA and MDS patients is significantly higher than that in normal control and hematologic malignancy group. OR value>1 showed a positive correlation between the diseases and HLA-DR15. HLA-DR15 is a susceptible gene in AA and MDS. The abnormalities of immunoglobulin level and ratios of T cell subsets in AA and MDS are common, but are not associated significantly with the expression of HLA-DR15.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anemia, Aplastic ; immunology ; metabolism ; Case-Control Studies ; Female ; Flow Cytometry ; HLA-DR Antigens ; immunology ; metabolism ; HLA-DR Serological Subtypes ; Histocompatibility Testing ; Humans ; Immunoglobulins ; immunology ; metabolism ; Male ; Middle Aged ; Myelodysplastic Syndromes ; immunology ; metabolism ; T-Lymphocyte Subsets ; immunology ; metabolism ; Young Adult

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 risk factors of hepatitis B virus (HBV) intrauterine infection.

METHODSRisk factors of HBV intrauterine infection were analyzed by nested case control study.

RESULTSData from univariate analysis revealed that risk factors of HBV intrauterine infection were positive results on HLA-DR3 (OR = 4.71, 1.62-13.66), HBV DNA (OR = 6.59, 2.72-15.97) and HBeAg (OR = 4.53, 1.93-10.64) in pregnant women, HLA-DR3 (OR = 3.91, 1.18-12.94) in newborn, HLA-I) R3 (OR = 5.96, 1.14-31.15) both in pregnant women and her newborns and HBV infection in placentas (OR = 2.51,1.12-5.60). Results from Multivariate unconditional logistics regression analysis showed that the risk factors of HBV intrauterine infection were positive in both HLA-DR3 (OR = 4.65, 1.44-15.05) and HBV DNA (OR = 6.56, 2.65-16.23) in pregnant women. However, there was no interaction between the two factors. The exposure rate of other factors did not reveal the difference in the two groups. With the increase of HBV DNA in pregnant women, the risk of HBV intrauterine infection was rising (chi2 = 16.74, P < 0.05).

CONCLUSIONRisk factors of HBV intrauterine infection were HLA-DR3 positive and HBV DNA positive in pregnant women but there was no interaction between the two factors. The risk of HBV intrauterine infection was increased along with the increase of HBV DNA in pregnant women.

Adult ; DNA, Viral ; genetics ; Female ; HLA-DR3 Antigen ; metabolism ; Hepatitis B ; virology ; Hepatitis B virus ; genetics ; physiology ; Humans ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; Logistic Models ; Pregnancy ; Pregnancy Complications, Infectious ; virology ; 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