Association of rare single nucleotide variant MUC5B rs35705950 with interstitial lung disease in Japanese rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) is sometimes complicated by interstitial lung disease (ILD) with a poor prognosis. A single nucleotide variant (SNV) in MUC5B was associated with ILD in European RA patients. However, associations of this SNV were not found in Japanese RA patients, because its frequency in Japanese populations is very low. We investigated the associations of candidate SNVs including the MUC5B variant with ILD in Japanese RA. METHODS: Genotyping of MUC5B rs35705950, MUC2 rs7934606, MAD1L1 rs12699415, and PPFIBP2 rs6578890 in Japanese RA patients was conducted for association analyses. RESULTS: MUC5B rs35705950 was associated with usual interstitial pneumonia (UIP) (p = 0.0039, Pc = 0.0156, odds ratio [OR] 10.66, 95% confidence interval [CI] 2.05-55.37) or ILD (p = 0.0071, Pc = 0.0284, OR 7.33, 95%CI 1.52-35.44) in Japanese RA under the allele model. MUC2 rs7934606 was associated with UIP (p = 0.0072, Pc = 0.0288, OR 29.55, 95%CI 1.52-574.57) or ILD (p = 0.0037, Pc = 0.0148, OR 22.95, 95%CI 1.27-416.13) in RA. Haplotype analyses suggested the primary association of MUC5B rs35705950 with UIP in Japanese RA. No significant association of MAD1L1 rs12699415 or PPFIBP2 rs6578890 with UIP, nonspecific interstitial pneumonia, or ILD in RA was observed. CONCLUSIONS: MUC5B rs35705950 is associated with, and might be involved in the pathogenesis of ILD, especially UIP, in Japanese RA.

Synovial fluid crystal analysis with compensated polarization using a gout analyser in clinical practice.

OBJECTIVE: To validate the gout analyzer as a clinical method of synovial fluid crystal analysis. METHODS: Thirty knee synovial fluid samples with suspected calcium pyrophosphate (CPP) crystals were analyzed. Within 48 hours after collection, each non-centrifuged sample was examined blindly and independently by one or more rheumatologists in the following order: 1) with an optical microscope under ordinary light, 2) with the same microscope under compensated polarization provided by a gout analyzer, and 3) with a fully equipped compensated polarized microscope with a rotating stage as the gold standard. As a reference, laboratory technicians analyzed fresh, centrifuged synovial fluid using a gout analyzer. RESULTS: Of the 30 samples analyzed, CPP and monosodium urate (MSU) crystals were detected in 11 and four, non-centrifuged samples, respectively, using a fully equipped compensated polarized microscope. The rheumatologists' detection rate of crystals in the non-centrifuged synovial fluid under ordinary light and with a gout analyzer was 73.3% and 80%, respectively. The laboratory technicians' detection rate in fresh centrifuged synovial fluid using a gout analyzer was 100%. CONCLUSION: A gout analyzer may be used to diagnose gout and calcium pyrophosphate deposition disease definitively if a fully equipped compensated polarized microscope is unavailable.

Efficacy of sulfasalazine for the prevention of Pneumocystis pneumonia in patients with rheumatoid arthritis: A multicentric self-controlled case series study.

INTRODUCTION: Pneumocystis pneumonia (PCP) is an opportunistic lung infection and has been reported among patients with rheumatoid arthritis (RA). An animal study revealed that sulfasalazine enhances Pneumocystis clearance from the lung by accelerating macrophage activity. METHODS: The self-controlled case series (SCCS) method was used to investigate the association between sulfasalazine use and PCP development in patients with RA without the effect of time-invariant, interpatient confounders. PCP episodes which developed in patients with RA at five hospitals between 2003 and 2019 were identified. PCP was defined by the following criteria: 1) detection of Pneumocystis jirovecii in respiratory specimens by polymerase chain reaction; 2) clinical symptoms (pyrexia, dry cough, dyspnea or hypoxia); 3) diffuse interstitial infiltrate on chest imaging; and 4) absence of PCP prophylaxis. The PCP incidence rate ratio (IRR) was compared between periods with and without sulfasalazine use by conditional Poisson regression. RESULTS: Fifty episodes of PCP were identified in 49 patients. Thirty patients received sulfasalazine at some point during their observation. While 49 episodes of PCP developed in 170.3 person-years without sulfasalazine use, only one episode of PCP developed in 103.7 person-years with sulfasalazine use. Sulfasalazine use was associated with a decreased PCP risk (adjusted IRR <0.01; 95% confidence interval <0.01-0.03) after adjusting for age and glucocorticoid, methotrexate, and tumor necrosis factor inhibitor administration. CONCLUSION: Our study demonstrated a preventive effect of sulfasalazine against PCP in patients with RA.

Pharmacokinetics of hydroxychloroquine in Japanese systemic lupus erythematosus patients with renal impairment.

OBJECTIVES: Reduction of the hydroxychloroquine (HCQ) dosage is recommended in systemic lupus erythematosus (SLE) patients with renal impairment, but a pharmacokinetics (PK) study of patients with renal impairment has not yet been performed. METHODS: We investigated the PK of both single and multiple doses of HCQ and its metabolites in SLE patients with renal impairment who newly started HCQ at a daily dose of 300 mg based on an ideal body weight dosage of 6.5 mg/kg. Population PK analysis was performed using a non-linear mixed-effects model. RESULTS: In total, 219 samples from 21 patients were analysed. The PK of HCQ in blood after single and multiple oral administrations followed the two-compartment model. At steady state, the concentration ratio of HCQ to each metabolite was HCQ:desethylhydroxychloroquine:desethylchloroquine:bisdesethylchloroquine = 1:0.28:0.1:0.06. The HCQ concentration correlated positively with that of each metabolite. The estimated values (relative standard error) of the population PK parameters were the total clearance at 110 l/h (31%) and a central volume of distribution of 398 l (19%). Co-administration of prednisolone and age, but not renal impairment, were factors affecting the total clearance of HCQ. CONCLUSIONS: From the PK perspective, a dosage reduction is unnecessary in SLE patients with impaired renal function.

Antibodies against Serum Anti-Melanoma Differentiation-Associated Gene 5 in Rheumatoid Arthritis Patients with Chronic Lung Diseases.

Chronic lung diseases (CLD), including interstitial lung disease (ILD) and airway diseases (ADs), are common complications of rheumatoid arthritis (RA). Rheumatoid factor (RF) and anti-citrullinated peptide antibodies are reported to be associated with CLD in RA patients. The presence of anti-melanoma differentiation-associated gene 5 (MDA5) antibodies (Abs) is associated with clinically amyopathic dermatomyositis developing into rapidly progressive ILD. However, few studies on anti-MDA5 Abs in RA have been published. Here, we analyzed the association of anti-MDA5 Abs with CLD complications in RA. Anti-MDA5 Abs were quantified in sera from RA patients with or without CLD. Anti-MDA5 Ab levels were higher in RA patients with ADs than without (mean ± SDM, 4.4 ± 2.4 vs. 4.0 ± 4.2, p = 0.0001). AUC values of anti-MDA5 Ab and RF ROC curves were similar in RA patients with or without CLD (0.578, 95%CI 0.530-0.627 and 0.579, 95%CI 0.530-0.627, respectively, p = 0.9411). Multiple logistic regression analysis of anti-MDA5 Abs and clinical characteristics yielded an MDA5-index with a higher AUC value than anti-MDA5 Ab alone (0.694, 95%CI 0.648-0.740, p = 5.08 × 10-5). Anti-MDA5 Abs were associated with ADs in RA patients and could represent a biomarker for CLD, similar to RF. The involvement of anti-MDA5 Abs in the pathogenesis of ADs in RA is proposed.

Serum rheumatoid factor IgA, anti-citrullinated peptide antibodies with secretory components, and anti-carbamylated protein antibodies associate with interstitial lung disease in rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is often complicated with chronic lung diseases (CLD), including interstitial lung disease (ILD) and airway disease, which occur as extra-articular manifestations. CLD in RA have been associated with the production of rheumatoid factor (RF), anti-citrullinated peptide antibody (ACPA), or anti-carbamylated protein (CarP) antibody. However, few validation studies have been performed thus far. In the present study, we investigated the association of RF, ACPA, and anti-CarP antibodies with RA complicated with CLD. METHODS: Sera from RA patients with or without CLD were collected. The levels of serum RF, RF immunoglobulin A (IgA), ACPA IgG, ACPA IgA, and ACPA secretory component (SC) were measured using enzyme-linked immunosorbent assay. RESULTS: The comparison of RA patients with and without CLD showed that RF IgA was associated with ILD (mean ± standard deviation: 206.6 ± 400.5 vs. 95.0 ± 523.1 U/ml, respectively, P = 1.13 × 10- 8), particularly usual interstitial pneumonia (UIP) (263.5 ± 502.0 U/ml, P = 1.00 × 10- 7). ACPA SC was associated with RA complicated with ILD (mean ± standard deviation: 8.6 ± 25.1 vs. 2.3 ± 3.4 U/ml, respectively, P = 0.0003), particularly nonspecific interstitial pneumonia (NSIP) (10.7 ± 31.5 U/ml, P = 0.0017). Anti-CarP antibodies were associated with RA complicated with ILD (0.042 ± 0.285 vs. 0.003 ± 0.011 U/ml, respectively, P = 1.04X10- 11). CONCLUSION: RF IgA and ACPA SC in RA were associated with UIP and NSIP, respectively, suggesting different specificities in patients with RA. Anti-CarP antibodies were associated with ILD in RA. These results may help elucidate the different pathogeneses of UIP and NSIP in RA.

Association of functional (GA)n microsatellite polymorphism in the FLI1 gene with susceptibility to human systemic sclerosis.

OBJECTIVE: Susceptibility genes that can account for characteristic features of SSc such as fibrosis, vasculopathy and autoimmunity remain to be determined. In mice, deficiency of Friend leukaemia integration 1 transcription factor (Fli1) causes SSc-like disease with these features. The human FLI1 gene contains (GA)n microsatellite, which has been shown to be associated with expression level. Because microsatellite polymorphisms are difficult to capture by genome-wide association studies, we directly genotyped FLI1 (GA)n microsatellite and examined its association with SSc. METHODS: Genomic DNA from 639 Japanese SSc patients and 851 healthy controls was genotyped for (GA)n microsatellite using the fragment assay. The cut-off repeat number for susceptibility to SSc was determined by receiver operating characteristics (ROC) analysis. Association with susceptibility and clinical characteristics was examined using logistic regression analysis. FLI1 mRNA levels were determined using quantitative RT-PCR. RESULTS: Based on the ROC analysis, (GA)n alleles with ≥22 repeats were collectively defined as L alleles and alleles with ≤21 repeats as S alleles. (GA)n L alleles were significantly associated with susceptibility to SSc (P = 5.0e-04, odds ratio 1.34, additive model). Significant association was observed both in diffuse cutaneous and limited cutaneous SSc. Among the SSc, (GA)n L alleles were significantly enriched in the patients with a modified Rodnan total skin thickness score ≥10 compared with those with a score <10. FLI1 mRNA levels were significantly decreased in healthy controls carrying (GA)n L alleles as compared with non-carriers. CONCLUSION: Extended repeat alleles of FLI1 (GA)n microsatellite may be associated with lower FLI1 mRNA levels and susceptibility to human SSc.

Utility of the neutrophil-to-lymphocyte ratio for predicting bacterial infection in patients with rheumatoid arthritis receiving Tocilizumab.

This study aimed to describe the utility of the neutrophil-to-lymphocyte ratio (NLR) for predicting bacterial infections in patients with rheumatoid arthritis (RA) treated with Tocilizumab (TCZ). We extracted RA patients treated with TCZ in whom an infection developed between April 2008 and March 2018 from our hospital database. We divided these patients into the bacterial infection and non-bacterial infection groups and compared their background, C-reactive protein (CRP) values, white blood cell count (WBC), the NLR at the time of infection diagnosis, and the ratio of the NLR at the time of infection diagnosis (post-NLR) to the NLR at baseline (pre-NLR). Of the 196 patients who received TCZ, 21 experienced a bacterial infection and 20 had a non-bacterial infection. The median CRP level, WBC count, post-NLR, and post-NLR/pre-NLR ratio in the bacterial infection group were significantly higher than in the non-bacterial infection group. In receiver operating characteristics (ROC) curve analysis for predicting bacterial infection, the area under the curve (AUC) for CRP, WBC, NLR, and the post-NLR/pre-NLR ratio were 0.787, 0.857, 0.887, and 0.975, respectively. The cut-off value of 2.25 for the post-NLR/pre-NLR ratio showed the greatest sensitivity (90.5%) and specificity (100%). The post-NLR/pre-NLR ratio may be a useful surrogate marker for predicting bacterial infections in patients with RA treated with TCZ.

Human leukocyte antigen in Japanese patients with idiopathic inflammatory myopathy.

Objective: The human leukocyte antigen (HLA) is the strongest genetic risk factor for idiopathic inflammatory myopathy (IIM), and different HLA alleles have been reported to be associated with IIM susceptibility among different ethnic groups. In this study, we have investigated HLA alleles associated with IIM in Japanese patients.Methods: Genotyping of HLA-DRB1 and DPB1 were performed in 252 Japanese IIM patients (166 dermatomyositis [DM] and 86 polymyositis [PM] patients) and the association was analyzed with comparison to controls (n = 1026 for DRB1 and n = 413 for DPB1).Results: DRB1*08:03 was associated with IIM (p = 1.60 × 10-5, pc = .0005, odds ratio [OR] 2.11, 95% confidence interval [CI] 1.52-2.92) and DM (p = .0004, pc = .0128, OR 2.06, 95%CI 1.40-3.02). DPB1*05:01 was also associated with IIM (p = .0001, pc = .0021, OR 1.96, 95%CI 1.38-2.77) and DM (p = .0005, pc = .0075, OR 2.05, 95%CI 1.37-3.08). DRB1*09:01 (p = .0012, pc = .0368, OR 0.35, 95% CI 0.18-0.69) and DPB1*04:01(p = .0004, pc = .0057, OR 0.05, 95% CI 0.00-0.85) were protectively associated with PM. Two locus analyses suggested that DRB1*09:01 and DPB1*04:01 were independently associated with PM.Conclusion: Protective associations of HLA were detected in Japanese PM patients.

Characteristics and risk factors of an emergency department visit in patients with systemic lupus erythematosus.

This study aimed to examine the characteristics of patients with systemic lupus erythematosus (SLE) visiting the emergency department (ED) and the risk factors of an ED visit by these patients. This 4-year retrospective study was performed at a tertiary care center in Japan. We included all 205 patients with SLE who were treated in our outpatient clinic between April 1, 2008 and March 31, 2012 and divided them into two groups: those who visited the ED (the ED-user group) and those who did not (the ED-non-user group). We statistically compared the patient backgrounds and characteristics of the groups and identified the risk factors of an ED visit. Of all the patients, 118 visited the ED during study period and 87 did not. In total, 269 events were identified in the ED-user group. Of these, 91 (33.8%) were cases of infection, 32 (11.9%) were orthopedic problems, 32 (11.9%) were cases of gastrointestinal disease, 31 (11.5%) were cases of neurological disease, and 25 (9.3%) were cardiovascular events. Twenty-four events (8.9%) were due to SLE flares, of which ten (41.7%) were cases of neuropsychiatric lupus (NPSLE). The glucocorticoid dosage and the presence of a psychiatric illness, NPSLE, and lupus nephritis were higher among the ED-user group. Multivariate logistic regression analysis demonstrated high glucocorticoid dosage to be a risk factor of an ED visit. Among SLE patients, infections were the principal reason for visiting the ED. The most common reasons for an ED visit were common diseases rather than flares.

Influence of seasonal changes on disease activity and distribution of affected joints in rheumatoid arthritis.

BACKGROUND: Previous studies suggest that RA activity is sensitive to seasonal changes. This study explored the influence of season on RA activity, particularly the distribution of affected joints, using a nationwide database in Japan. METHODS: We investigated 12,839 patients whose RA activity was recorded in spring (n = 3250), summer (n = 916), fall (n = 1021), and winter (n = 7652). Disease activity score (DAS) 28-CRP, simplified disease activity index (SDAI), and clinical disease activity index (CDAI) were used as indices of disease activity. Disease activity was also assessed according to DAS28-CRP scores (remission, low, moderate, or high). The affected joint distribution was investigated using novel joint indices (x, y, z), where x and y are indices for the upper and lower joints, respectively, and z is the index for large joint predominance. RESULTS: Mean DAS28-CRP and median SDAI and CDAI scores were highest in spring and lowest in fall. There was a significant difference in the DAS28-CRP for fall versus spring and winter. Fall was associated with a higher remission rate, and spring and winter with high and moderate RA activity, respectively. Significant differences in x, y, SDAI, and CDAI scores were found for spring versus summer, fall, and winter, in addition to fall versus winter (except in y). There was no seasonal difference in the z index. CONCLUSIONS: RA activity in the upper and lower extremities may be highest in spring, followed by winter. Seasonal changes should be considered in patients with RA to better understand their symptoms.

Comparison of the clinical characteristics and severity of community-acquired pneumonia between patients with rheumatoid arthritis treated with tocilizumab and those treated with TNF inhibitor.

Objective: To examine the clinical characteristics and severity of community-acquired pneumonia (CAP) between patients with rheumatoid arthritis (RA) treated with tocilizumab (TCZ) and those treated with TNF inhibitors. Methods: We extracted RA patients treated with biological DMARDs who developed CAP between 2003 and 2015 from our hospital database. We compared the patient backgrounds, duration from the onset of symptoms to diagnosis, and the severity of CAP between patients who developed CAP after treatment with TCZ or tumor necrosis factor (TNF) inhibitor. Results: Of 98 patients who received TCZ, seven developed CAP (IL-6 inhibitor group). Of 560 patients who received TNF inhibitors, 27 developed CAP (TNF inhibitor group). Between the two groups, there was no difference in the duration from the onset of symptoms to diagnosis (7 [4-21], 7 days [1-15]). The IL-6 inhibitor group had a lower body temperature (36.5 °C [36.4-36.8], 37.8 °C [35.9-40.5]) and CRP level (0.09 mg/dL [0.02-2.5], 6.76 mg/dL [0.63-15.2]) at diagnosis than the TNF inhibitor group. The CURB-65 score did not differ significantly between groups. Conclusion: There were no delays in the diagnosis of CAP or any difference in the severity of CAP between patients with RA treated with TCZ and those treated with TNF-inhibitors.

Effect of sulfasalazine use on the presence of Pneumocystis organisms in the lung among patients with rheumatoid arthritis: A test-negative design case-control study with PCR tests.

OBJECTIVE: To evaluate the effect of sulfasalazine (SSZ) on the presence of Pneumocystis jirovecii (P. jirovecii) in the lungs of rheumatoid arthritis (RA) patients. METHODS: We retrospectively studied episodes of suspected P. jirovecii pneumonia (PJP) which were examined for P. jirovecii with polymerase chain reaction (PCR). We employed a test negative design case-control study; the cases were episodes of suspected PJP that were positive for PCR, and the controls were episodes of suspected PJP that were negative for PCR. The odds ratio for the positive PCR result associated with SSZ use was estimated by Firth's logistic regression. RESULTS: Between 2003 and 2017, 36 cases and 83 controls were identified. While none of the cases received SSZ before the episode, 18 of the controls received the drug. In the primary analysis involving all the episodes, SSZ use was negatively associated with PCR positivity (adjusted odds ratio, 0.087; confidence interval, <0.001-0.789). The sensitivity analysis, excluding those who received PJP prophylaxis, showed the same association as the primary analysis (adjusted odds ratio 0.085, 95% CI <0.001-0.790). CONCLUSION: This study demonstrated that SSZ use is associated with the absence of P. jirovecii in the lung, suggesting the preventive efficacy of the drug against PJP.

Biomarker for nontuberculous mycobacterial pulmonary disease in patients with rheumatoid arthritis: Anti-glycopeptidolipid core antigen immunoglobulin A antibodies.

OBJECTIVE: Nontuberculous mycobacterial (NTM) pulmonary disease is occasionally associated with rheumatoid arthritis (RA), influencing the therapeutic strategy of RA. Since chronic lung diseases are frequently associated with RA, the diagnosis of NTM pulmonary disease is quite difficult in RA patients. Recently, a serological diagnostic test detecting serum immunoglobulin A against the glycopeptidolipid (GPL) core antigen was developed. We investigated the serum levels of anti-GPL antibodies in RA patients to determine the usefulness for detecting NTM pulmonary disease. METHODS: Anti-GPL antibodies were detected in the sera from RA patients with or without NTM pulmonary disease. RESULTS: The positivity of anti-GPL antibodies in RA patients with NTM pulmonary disease was higher than in RA without (p = 1.76 × 10-14, odds ratio 70.29, 95% confidence interval [CI] 22.28-221.83). Anti-GPL Ab titers were increased in RA with NTM pulmonary disease (mean titer ± standard deviation [U/ml], RA with NTM pulmonary disease: 4.1 ± 7.0, RA without NTM pulmonary disease: 0.4 ± 1.6, p = 1.51 × 10-10). The area under the curve (AUC) value of the receiver operating characteristic (ROC) curve for anti-GPL antibodies was 0.917 (95%CI 0.860-0.974, p = 3.32 × 10-47). CONCLUSIONS: Serum anti-GPL antibodies are useful for detecting NTM pulmonary disease in RA patients.

Plasma miRNA expression profiles in rheumatoid arthritis associated interstitial lung disease.

BACKGROUND: Interstitial lung disease (ILD) is frequently associated with rheumatoid arthritis (RA), and is designated RA-associated ILD (RA-ILD). RA-ILD has a large impact on the prognosis of RA. Here, we investigated the micro RNAs (miRNAs) profiles to determine whether they may be useful for diagnosing RA-ILD. METHODS: RNA was isolated from plasma samples and cDNA was synthesized. Real-time RT-PCR analysis was performed to evaluate 752 miRNA expression profiles in plasma pools from RA patients with or without RA-ILD. Sixteen selected miRNA levels were analyzed in individual plasmas from 64 RA patients with or without RA-ILD. RESULTS: Expression levels of hsa-miR-214-5p (mean relative expression level ± standard deviation, 8.1 ± 28.2 in RA with ILD, 0.2 ± 0.9 in RA without ILD, P = 0.0156) and hsa-miR-7-5p (56.2 ± 260.4 in RA with ILD, 4.7 ± 11.8 in RA without ILD, P = 0.0362) were higher in RA patients with RA-ILD than in those without. The values of miRNA index (214, 7) generated from hsa-miR-214-5p and hsa-miR-7-5p for ILD were significantly elevated in RA patients with RA-ILD compared with those without (0.122 ± 0.332 in RA with ILD, 0.006 ± 0.013 in RA without ILD, P = 0.0010). The area under the curve value of the receiver operating characteristic curve for the miRNA index (214, 7) was 0.740. CONCLUSIONS: To the best of our knowledge, this is the first report of miRNA profiles in RA-ILD. The expression levels of hsa-miR-214-5p and hsa-miR-7-5p were increased in RA with ILD.

Association of human leukocyte antigen alleles with chronic lung diseases in rheumatoid arthritis.

OBJECTIVES: Chronic lung diseases including interstitial lung disease and airway disease (AD) occur in RA patients. Interstitial lung disease and AD in RA are extra-articular manifestations that influence the prognosis quoad vitam of RA. Studies on associations of HLA alleles with RA have been carried out, and shared epitopes of several alleles are reported to be associated with RA susceptibility. Few association studies in RA subpopulations with chronic lung diseases have been conducted. The aim of the study was to identify HLA alleles predisposing to RA phenotypes including the presence of AD. METHODS: Associations of HLA-DRB1 and DQB1 alleles with chronic lung diseases in RA were analysed. RESULTS: A positive association was found between the DR4 serological group and resistance to usual interstitial pneumonia [P = 0.0250, odds ratio (OR) 0.62, 95% CI: 0.41, 0.93]. The DR2 serological group was associated with susceptibility to usual interstitial pneumonia (P = 0.0036, OR = 1.86, 95% CI: 1.23, 2.81). An association was found for shared epitopes alleles with bronchiolitic AD (P = 0.0040, OR = 2.06, 95% CI: 1.24, 3.41). DQB1*03:01 was associated with bronchiectatic AD (P = 0.0021, corrected P-value (Pc) = 0.0315, OR = 1.99, 95% CI: 1.30, 3.06), as well as with emphysema (P = 0.0007, Pc = 0.0104, OR = 2.43, 95% CI: 1.49, 3.95). In combined analysis, a predisposing association of DQB1*03:01 (P = 1.94 ×10(-5), Pc = 0.0003, OR = 2.16, 95% CI: 1.53, 3.06) and a negative association of DQB1*03:02 (P = 0.0008, Pc = 0.0117, OR = 0.33, 95% CI: 0.17, 0.67) with bronchiectatic AD or emphysema were observed in RA. CONCLUSION: The present study identified an association of HLA-DQB1*03:01 with predisposition to, and DQB1*03:02 with resistance to, bronchiectatic AD or emphysema in RA.

Severe Thrombocytopenia Induced by First Infliximab Administration for Rheumatoid Arthritis.

Thrombocytopenia due to antitumor necrosis factorα agents is very rare. A 68-year-old woman with rheumatoid arthritis on methotorexate received infliximab (IFX). Three days after the first IFX infusion, she developed gingival bleeding, petechia, and gross hematuria. Her platelet count fell to 2000/µL. We administered a platelet transfusion and intravenous methylprednisolone. Three days after admission, her platelet count was 7000/µL and her bleeding persisted. After double filtration plasmapheresis, her bleeding stopped and her platelet count recovered over 2 weeks. Thrombocytopenia is a rare but severe complication of IFX. Double filtration plasmapheresis may be useful for removing IFX or possible antibodies against platelets when IFX remaining in the patient's blood interferes with improvement of the patient's condition.

MMP-3 can distinguish isolated PMR from PMR with GCA: A retrospective study regarding PMR and GCA in Japan.

OBJECTIVE: We sought to identify clinical features at diagnosis that can distinguish isolated polymyalgia rheumatica (PMR) without giant cell arteritis (GCA) from PMR with GCA, and clinical features at diagnosis of isolated PMR that can predict subsequent relapse and corticosteroid discontinuation. METHODS: A retrospective study of 115 patients with isolated PMR and 29 patients with GCA was performed. A comparison between isolated PMR patients, GCA patients (with or without PMR), and PMR with GCA patients was performed. Predictors of relapse and corticosteroid discontinuation were identified using a logistic regression in the patients with isolated PMR. RESULTS: Matrix metalloproteinase-3 (MMP-3) level was significantly different among the patient groups. MMP-3: 230.5 ± 201.5 ng/mL in isolated PMR, 80.5 ± 47.5 ng/mL in GCA (p < 0.01), and 96.8 ± 54.8 ng/mL in PMR with GCA (p = 0.03). In the patients with isolated PMR, female gender (odds ratio [OR], 2.73; 95% confidence interval [CI], 1.16-6.41; p < 0.05) and creatinine (Cr) < 50 µmol/L (OR, 2.48; 95% CI, 1.02-5.99; p < 0.05) were significant prognostic factors that predicted relapse. CONCLUSION: A low level of MMP-3 is an excellent positive predictor for PMR with GCA. Among patients with isolated PMR, female gender and Cr < 50 µmol/L were significant prognostic factors that predicted relapse.

Human leukocyte antigen polymorphisms and personalized medicine for rheumatoid arthritis.

Human leukocyte antigen (HLA) polymorphisms are the most important genetic risk factors for rheumatoid arthritis (RA), a chronic systemic inflammatory disease of unknown etiology. Certain HLA-DRB1 alleles, known as shared epitope (SE) alleles because they have the same amino-acid sequence at positions 70-74, are associated with susceptibility to RA. A gene dosage effect is present for RA-predisposing SE alleles, and protective alleles show epistasis. An important role of amino-acid polymorphisms at positions 11 and 13 of the HLA-DRß chain was also reported recently. Rheumatoid factor and anticitrullinated peptide antibodies are present in many RA patients. Similar to extra-articular manifestations, the presence of these autoantibodies is also associated with certain DRB1 alleles. Different frequencies of RA risk alleles in different ethnicities explain the varying prevalence of RA in different populations and suggest genetic heterogeneity of RA with regard to phenotype and population subsets. Some drug-induced hypersensitivity reactions due to disease-modifying antirheumatic drugs are also associated with HLA alleles. Understanding the role of HLA as the most important genetic factor relevant to RA susceptibility may help in determining its pathogenesis and pave the way to personalized medicine.