Deciphering the association between biopsy-confirmed systemic small vessel vasculitis and Epstein-Barr virus-positive polymorphic B-cell lymphoproliferation.

The Epstein-Barr virus (EBV) is associated with various lymphoproliferative disorders (LPD). Additionally, EBV infection has correlated with diverse autoimmune diseases. However, the association between EBV and systemic small vessel vasculitis (SVV) remains controversial. Here, we report a case of SVV with pauci-immune glomerulonephritis accompanied by an EBV-positive polymorphic B-cell LPD, not otherwise specified. The intricate distinction between EBV-positive B-cell LPD and SVV was difficult, as both diseases demonstrated similar clinical presentations. Lymph node and kidney biopsies facilitated the accurate diagnosis of these two conditions. The administration of high-dose prednisolone, combined with rituximab, proved efficacious, with no instances of relapse over the subsequent 2-year period. This case indicates an association between EBV-positive B-cell LPD and SVV. The diligent execution of biopsies is a crucial diagnostic and interpretive strategy, generating precise comprehension of this condition and guiding its appropriate therapeutic management.

Effectiveness of intravenous methylprednisolone pulse in patients with severe microscopic polyangiitis and granulomatosis with polyangiitis.

OBJECTIVES: To evaluate the effectiveness and safety of two different intravenous methylprednisolone (IVMP) pulse doses in patients with severe microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). METHODS: We emulated a target trial using observational data from the nationwide registry in Japan. Patients with severe glomerulonephritis or diffuse alveolar haemorrhage were selected and pseudo-randomized into three groups using propensity score-based overlap weighting as follows: non-IVMP, IVMP 0.5 g/day and IVMP 1.0 g/day. The primary outcome was all-cause mortality, and the secondary outcomes were composite all-cause mortality and kidney failure, severe relapse and serious infection from 2 to 48 weeks after treatment initiation. To estimate the treatment effects, the Cox proportional hazard model and Fine-Gray subdistribution hazard model were used. RESULTS: In this emulated target trial, of 201 eligible patients (MPA, 175; GPA, 26), 6 (3%) died, 4 (2.0%) had kidney failure, 11 (5.5%) had severe relapse, and 40 (19.9%) had severe infections. Hazard ratios (HR) for IVMP 0.5 g/day and IVMP 1.0 g/day pulse groups compared with non-IVMP pulse were as follows: all-cause mortality 0.46 (95% CI: 0.07, 2.81) and 0.07 (95% CI: 0.01, 0.41), respectively; all-cause mortality/kidney failure 1.18 (95% CI: 0.26, 5.31) and 0.59 (95% CI: 0.08, 4.52), respectively; subdistribution HRs for severe relapse were 1.26 (95% CI: 0.12, 13.70) and 3.36 (95% CI: 0.49, 23.29), respectively; and for serious infection 1.88 (95% CI: 0.76, 4.65) and 0.94 (95% CI: 0.28, 3.13), respectively. CONCLUSION: IVMP 1.0 g/day pulse may improve 48-week mortality in patients with severe MPA/GPA.

Association between early immunophenotypic changes and therapeutic response of belimumab in patients with systemic lupus erythematosus.

Belimumab is a therapeutic medication that inhibits the B-cell-activating factor (BAFF) used for systemic lupus erythematosus (SLE); however, the response sometimes varies among individuals, even when patients are stratified based on general clinical characteristics. Therefore, we focused on immunological phenotypic changes with belimumab, investigated their association with subsequent clinical courses, and sought to identify relevant immunological indicators to stratify patients who would benefit from belimumab. We assessed changes in B and T cell phenotypes, as well as BAFF-related factors, such as levels of BAFF and a proliferation-inducing ligand, and expression of three BAFF receptors: BAFF receptor (BAFF-R), B-cell maturation antigen (BCMA), transmembrane activator and cyclophilin ligand interactor (TACI), in 19 patients with SLE who were treated with belimumab before and 3 months after treatment. First, to visualize patterns in complex and diverse data, we summarized B cell changes such as subsets and BAFF receptor expressions into two axes, the first and second principal components (PC1 and PC2), and characterized broad phenotypic changes by cluster analysis. Next, we evaluated whether the B cell changes represented by PC1 and PC2 were associated with other concurrent phenotypic changes, baseline factors, and treatment response at 6 months. We found that lower PC2, indicating increased BAFF-R expression and decreased percentage of naïve B cells, was associated with a subsequent therapeutic response at 6 months (odds ratio 5.3, 95% confidence interval 1.2-24, p = .031). Furthermore, higher percentages of effector memory CD3+CD4+ T cells at baseline were associated with lower PC2 and therapeutic response. Further analysis revealed that increased PC1, as reflected by increased BCMA and TACI expression and an increase in the percentage of class-switched memory B cells, was associated with both T and B cell activation. Although belimumab is a B-cell targeted therapy, it can also influence T-cell phenotypes. Thus, early B cell changes could be used to predict treatment response, and their changes could be predicted from baseline T cell phenotypes, indicating the importance of B and T cell interactions.

Non-drug and surgical treatment algorithm and recommendations for the 2020 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis-secondary publication.

OBJECTIVES: The aim of this study was to update the Japan College of Rheumatology (JCR) clinical practice guidelines (CPGs) for the management of rheumatoid arthritis (RA) and prepare an algorithm for non-drug and surgical treatments. This article is a digest version of the guidelines. METHODS: The Japanese Ministry of Health, Labour and Welfare's research group, in collaboration with the JCR, used the Grading of Recommendations, Assessment, Development, and Evaluation method to update the 2014 JCR CPG for RA. The consensus was formed by CPG panel members. RESULTS: We raised 19 clinical questions regarding non-drug and surgical treatments for RA and developed recommendations. The treatments included exercise therapy; occupational therapy; joint injection of corticosteroids; and orthopaedic surgeries including cervical spine surgery, wrist and foot arthroplasty, ankle arthrodesis, and replacement arthroplasty of the shoulder, elbow, finger, hip, knee, and ankle. Recommendations regarding the risks of surgery and perioperative discontinuation of medications have also been developed. Based on these recommendations, we created an original algorithm for the non-drug and surgical treatment of RA. CONCLUSIONS: These recommendations are expected to serve rheumatologists, health care professionals, and patients with RA as tools for shared decision-making to treat residual limb joint symptoms and functional impairment.

Patient satisfaction with total joint replacement surgery for rheumatoid arthritis: a questionnaire survey for the 2020 update of the Japan college of rheumatology clinical practice guidelines.

OBJECTIVE: This study aimed to evaluate satisfaction with total joint replacement (TJR) surgery among patients with rheumatoid arthritis (RA). METHODS: We mailed questionnaires to randomly selected members of the Japan Rheumatism Friendship Association, stratified by age and prefecture, throughout Japan. The questionnaire collected demographic and clinical characteristics as well as patients' satisfaction with TJR and their current therapy. RESULTS: Of the 1156 patients who returned the questionnaire, 339 (29.3%) responded that they had had TJR of any type. The mean age was 66.6 years, and 94.4% were women. The mean time period from the hip and knee TJR was 14-15 years. Over half of the patients who had had TJR were satisfied with the results, especially those who had had hip (89.6%) and knee TJR (87.3%), who reported a high level of satisfaction. Multivariable linear regression analysis revealed that, in patients with knee TJR, satisfaction with current therapy was significantly related to whether they were satisfied with the results of the surgery. CONCLUSION: Most patients with RA who had undergone TJR were satisfied with the results even after a long period of time, and their level of satisfaction was associated with their satisfaction with current therapy.

Systematic review for the treatment of older rheumatoid arthritis patients informing the 2020 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis.

OBJECTIVES: To provide an evidence base for clinical practice guidelines (CPG) for the management of rheumatoid arthritis (RA) in older adults. METHODS: PubMed, Cochrane library, and Japan Centra Revuo Medicina databases were searched for articles published between 1990 and 2019. Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation system, with some modifications. RESULTS: Among 702 identified articles, there were 5 post-hoc analyses of randomized controlled trials and 10 observational studies. Meta-analysis of the former yielded a mean difference of the van der Heijde-modified total Sharp score of -2.79 (95% confidence interval [CI] - 3.74 to -1.84) for treatment with tumor necrosis factor inhibitors. The risk ratio (RR) for the American College of Rheumatology 50% response rate, and for serious adverse events was 2.83 (95%CI 1.90-4.21) and 1.32 (95%CI 0.53-3.31), respectively, for Janus kinase inhibitors. Meta-analysis of the observational studies yielded an RR for disease activity score-28 remission and serious infections of 0.76 (95%CI 0.64-0.91) and 1.92 (95%CI 1.31-2.81) for older-versus-younger patients receiving biological disease-modifying antirheumatic drugs, respectively. CONCLUSION: This systematic review provides the necessary evidence for developing CPG for the management of RA in older adults.

Comprehensive risk analysis of postoperative complications in patients with rheumatoid arthritis for the 2020 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis.

OBJECTIVES: To examine the risk factors of surgical site infection (SSI), delayed wound healing, and death after orthopedic surgery in patients with rheumatoid arthritis (RA). METHODS: We identified articles indexed in the Cochrane Library, PubMed, and Japan Centra Revuo Medicina Web published from 2013 to 2019 and other articles. Articles fulfilling the predefined inclusion criteria were reviewed systematically and their quality was appraised according to the Grading of Recommendations Assessment, Development, and Evaluation system with some modifications. RESULTS: After inclusion and exclusion by full-text review, 29 articles were analyzed. Use of biological disease modifying antirheumatic drugs was a risk factor of SSI (risk ratio 1.66, 95% confidence interval 1.25-2.19), but not of delayed wound healing. RA itself was a risk factor of SSI, and oral glucocorticoid use was a risk factor of SSI in three of the four studies analyzed and of postoperative death. Age, male sex, comorbidities such as diabetes mellitus and chronic obstructive pulmonary disease, surgical factors such as foot/ankle and spine surgery and longer operative time were risk factors of those postoperative complications. CONCLUSION: Patients with those factors should be dealt with appropriate cautions to strike a risk-benefit balance of orthopedic surgeries.

Upregulation of sphingosine-1-phosphate receptor 3 on fibroblast-like synoviocytes is associated with the development of collagen-induced arthritis via increased interleukin-6 production.

BACKGROUND: Sphingosine-1-phosphate receptor 3 (S1P3) is one of five receptors for sphingosine-1-phosphate (S1P). S1P/S1P3 signaling is involved in numerous physiological and pathological processes including bone metabolism, sepsis, cancer, and immunity. In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLSs) are activated by several factors and promote abundant proinflammatory cytokine production and bone destruction. The aim of this study was to investigate whether S1P3 is associated with the development of autoimmune arthritis and the pathogenic function of FLSs. METHODS: Wild-type (WT) and S1P3 knockout (S1P3-KO) collagen-induced arthritis (CIA) mice were evaluated with respect to clinical and histological disease severity, along with the levels of anti-collagen antibodies and expression of tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6). S1P3 expression in the synovium was analyzed by real-time reverse-transcription polymerase chain reaction (RT-PCR) and immunofluorescence staining. FLSs isolated from CIA mice were activated with TNFα and S1P3 expression was analyzed by real-time RT-PCR. The role of S1P/S1P3 signaling in activated and non-activated FLSs was investigated by measuring cell proliferation and cyto/chemokine production by real-time RT-PCR and/or enzyme-linked immunosorbent assay. RESULTS: Clinical and histological scores, and synovial IL-6 expression were significantly lower in S1P3-KO mice with CIA than in WT mice. Arthritic synovia had higher S1P3 expression than intact synovia and FLSs in arthritic joints expressed S1P3 in vivo. Primary cultured FLSs produced IL-6 in a time-dependent manner in response to S1P stimulation and exhibited higher levels of S1P3 expression after activation with TNFα. S1P3-induced production of IL-6 and MMP-3 was increased in FLSs pre-activated with TNFα. CONCLUSION: In this study, we demonstrated that S1P3 expression is associated with the development of autoimmune arthritis via inflammation-induced increases in S1P/S1P3 signaling that increase production of IL-6 in FLSs. Inhibition of S1P/S1P3 signaling could open the door to the development of new therapies for RA.

Roles of high-mobility group box 1 and thrombin in murine pulmonary fibrosis and the therapeutic potential of thrombomodulin.

Cross talk between inflammation and coagulation plays important roles in acute or subacute progressive pulmonary fibrosis characterized by diffuse alveolar damage. Thrombomodulin is a physiological inhibitor of high-mobility group box 1 (HMGB1), and thrombin and may be effective for this condition. This study investigated the roles of HMGB1 and thrombin in the pathophysiology of bleomycin-induced pulmonary fibrosis and the efficacy of recombinant human soluble thrombomodulin (rhTM). Pulmonary fibrosis was induced in wild-type C57BL/6 mice by intratracheal instillation of bleomycin. We first assessed HMGB1, thrombin, transforming growth factor (TGF)-ß1, and α-smooth muscle actin (SMA) levels in bronchoalveolar lavage fluid and lung tissue sections over time. Expression of HMGB1 and thrombin was elevated before that of TGF-ß1 and α-SMA and remained high during the fibrotic phase after bleomycin instillation. We next examined whether in vitro stimulation with HMGB1 and thrombin induced expression of TGF-ß1 and α-SMA in cultured alveolar macrophages and lung fibroblasts, respectively, by performing quantitative PCR, enzyme-linked immunosorbent assay, Western blot, and immunofluorescence analyses. HMGB1 and thrombin stimulation induced TGF-ß1 production by alveolar macrophages, and thrombin stimulation also induced α-SMA expression in lung fibroblasts. Finally, we evaluated the effect of rhTM on bleomycin-induced pulmonary fibrosis. Compared with the vehicle control, both early and late-phase administration of rhTM suppressed the fibrotic process. Our results suggest that HMGB1 and thrombin were involved in the pathophysiology of pulmonary fibrosis via production of profibrotic proteins and that rhTM attenuated bleomycin-induced pulmonary fibrosis. rhTM may be a therapeutic option for acute or subacute pulmonary fibrosis.

Role of allograft inflammatory factor-1 in bleomycin-induced lung fibrosis.

Allograft inflammatory factor-1 (AIF-1) is a protein expressed by macrophages infiltrating the area around the coronary arteries in a rat ectopic cardiac allograft model. We previously reported that AIF-1 is associated with the pathogenesis of rheumatoid arthritis and skin fibrosis in sclerodermatous graft-versus-host disease mice. Here, we used an animal model of bleomycin-induced lung fibrosis to analyze the expression of AIF-1 and examine its function in lung fibrosis. The results showed that AIF-1 was expressed on lung tissues, specifically macrophages, from mice with bleomycin-induced lung fibrosis. Recombinant AIF-1 increased the production of TGF-ß which plays crucial roles in the mechanism of fibrosis by mouse macrophage cell line RAW264.7. Recombinant AIF-1 also increased both the proliferation and migration of lung fibroblasts compared with control group. These results suggest that AIF-1 plays an important role in the mechanism underlying lung fibrosis, and may provide an attractive new therapeutic target.

Allograft inflammatory factor-1 in the pathogenesis of bleomycin-induced acute lung injury.

Allograft inflammatory factor-1 (AIF-1) is a protein expressed by macrophages infiltrating the area around the coronary arteries of rats with an ectopic cardiac allograft. Some studies have shown that expression of AIF-1 increased in a mouse model of trinitrobenzene sulfonic acid-induced acute colitis and in acute cellular rejection of human cardiac allografts. These results suggest that AIF-1 is related to acute inflammation. The current study used bleomycin-induced acute lung injury to analyze the expression of AIF-1 and to examine its function in acute lung injury. Results showed that AIF-1 was significantly expressed in lung macrophages and increased in bronchoalveolar lavage fluid from mice with bleomycin-induced acute lung injury in comparison to control mice. Recombinant AIF-1 increased the production of IL-6 and TNF-α from RAW264.7 (a mouse macrophage cell line) and primary lung fibroblasts, and it also increased the production of KC (CXCL1) from lung fibroblasts. These results suggest that AIF-1 plays an important role in the mechanism underlying acute lung injury.

Inhibition of osteoclastogenesis by osteoblast-like cells genetically engineered to produce interleukin-10.

Bone destruction at inflamed joints is an important complication associated with rheumatoid arthritis (RA). Interleukin-10 (IL-10) may suppress not only inflammation but also induction of osteoclasts that play key roles in the bone destruction. If IL-10-producing osteoblast-like cells are induced from patient somatic cells and transplanted back into the destructive bone lesion, such therapy may promote bone remodeling by the cooperative effects of IL-10 and osteoblasts. We transduced mouse fibroblasts with genes for IL-10 and Runx2 that is a crucial transcription factor for osteoblast differentiation. The IL-10-producing induced osteoblast-like cells (IL-10-iOBs) strongly expressed osteoblast-specific genes and massively produced bone matrix that were mineralized by calcium phosphate in vitro and in vivo. Culture supernatant of IL-10-iOBs significantly suppressed induction of osteoclast from RANKL-stimulated Raw264.7 cells as well as LPS-induced production of inflammatory cytokine by macrophages. The IL-10-iOBs may be applicable to novel cell-based therapy against bone destruction associated with RA.

Allograft inflammatory factor-1 stimulates chemokine production and induces chemotaxis in human peripheral blood mononuclear cells.

Allograft inflammatory factor-1 (AIF-1) is expressed by macrophages, fibroblasts, endothelial cells and smooth muscle cells in immune-inflammatory disorders such as systemic sclerosis, rheumatoid arthritis and several vasculopathies. However, its molecular function is not fully understood. In this study, we examined gene expression profiles and induction of chemokines in monocytes treated with recombinant human AIF (rhAIF-1). Using the high-density oligonucleotide microarray technique, we compared mRNA expression profiles of rhAIF-1-stimulated CD14(+) peripheral blood mononuclear cells (CD14(+) PBMCs) derived from healthy volunteers. We demonstrated upregulation of genes for several CC chemokines such as CCL1, CCL2, CCL3, CCL7, and CCL20. Next, using ELISAs, we confirmed that rhAIF-1 promoted the secretion of CCL3/MIP-1α and IL-6 by CD14(+) PBMCs, whereas only small amounts of CCL1, CCL2/MCP-1, CCL7/MCP-3 and CCL20/MIP-3α were secreted. Conditioned media from rhAIF-1stimulated CD14(+) PBMCs resulted in migration of PBMCs. These findings suggest that AIF-1, which induced chemokines and enhanced chemotaxis of monocytes, may represent a molecular target for the therapy of immune-inflammatory disorders.

Low body mass index is associated with impaired quality of life in patients with rheumatoid arthritis.

AIM: To investigate the relationship between quality of life (QOL) and rheumatoid chachesia, malnutrition in patients with rheumatoid arthritis (RA). METHODS: EuroQol Group 5-Dimension Self-Report Questionnaire (EQ5D) and Japanese Health Assessment Questionnaire (JHAQ) scores, body mass index (BMI), arm muscle area (AMA) and clinical indicators were measured in 385 RA patients. One-way analysis of variance for obtained data was conducted among three groups: 131 with low BMI (< 20), 163 with moderate (20-25) and 91 with high BMI (≥25). Then multiple regression analyses for JHAQ and EQ5D scores with nutritional and clinical indicators as independent variables were performed. RESULTS: EQ5D and JHAQ scores were significantly lower and higher, respectively, in the low BMI group than those in the moderate BMI group. Clinical indicators including doses of corticosteroid were similar among the three groups except for disease duration. Disease activity score (DAS) 28, disease duration, C-reactive protein and AMA were significant variables in the regression model for EQ5D. CONCLUSION: Low BMI deteriorates the QOL of RA patients. Muscle protein loss apparently leads to a reduction in BMI and QOL.

Myeloid-derived suppressor cells play crucial roles in the regulation of mouse collagen-induced arthritis.

Myeloid-derived suppressor cells (MDSCs) are of myeloid origin and are able to suppress T cell responses. The role of MDSCs in autoimmune diseases remains controversial, and little is known about the function of MDSCs in autoimmune arthritis. In this study, we clarify that MDSCs play crucial roles in the regulation of proinflammatory immune response in a collagen-induced arthritis (CIA) mouse model. MDSCs accumulated in the spleens of mice with CIA when arthritis severity peaked. These MDSCs inhibited the proliferation of CD4(+) T cells and their differentiation into Th17 cells in vitro. Moreover, MDSCs inhibited the production of IFN-γ, IL-2, TNF-α, and IL-6 by CD4(+) T cells in vitro, whereas they promoted the production of IL-10. Adoptive transfer of MDSCs reduced the severity of CIA in vivo, which was accompanied by a decrease in the number of CD4(+) T cells and Th17 cells in the draining lymph nodes. However, depletion of MDSCs abrogated the spontaneous improvement of CIA. In conclusion, MDSCs in CIA suppress the progression of CIA by inhibiting the proinflammatory immune response of CD4(+) T cells. These observations suggest that MDSCs play crucial roles in the regulation of autoimmune arthritis, which could be exploited in new cell-based therapies for human rheumatoid arthritis.

The rapid efficacy of abatacept in a patient with rheumatoid vasculitis.

We report a case of rheumatoid vasculitis (RV) that responded well to abatacept, a cytotoxic T lymphocyte-associated antigen 4 (CTLA4)-immunoglobulin fusion protein. A 38-year-old woman developed RV despite treatment with methotrexate and tumor necrosis factor (TNF) inhibitors. The effects of steroid therapy, immunoabsorption plasmapheresis, and interleukin-6 inhibitor were insufficient, however, administration of abatacept rapidly improved her clinical symptoms with almost normalization of the immunological findings. This is the first published case report of the successful treatment of RV with abatacept.

Mucin from rheumatoid arthritis synovial fluid enhances interleukin-6 production by human peripheral blood mononuclear cells.

The carbohydrate chains represented by mucins (MUCs) are expressed by a variety of normal and malignant secretory epithelial cells and induce a variety of immunoreactions. To find new mucins related to the pathogenesis of rheumatoid arthritis (RA), we examined high-molecular-weight molecules inducing cytokines on human peripheral blood mononuclear cells (PBMCs) in synovial fluid from affected joints. We found a high-molecular-weight substance that induces interleukin 6 production on PBMCs in RA synovial fluid on gel filtration. MUC-1 was present in the resulting fractions, although they had been purified by CsCl density gradient centrifugation. We also found that MUC-1 was expressed on synovial cells and infiltrating inflammatory mononuclear cells on the sublining layer and lymphoid follicles in RA synovial tissues. CD68-positive superficial synovial cells colocalized with MUC-1 and CD68-positive macrophages were in contact with MUC-1-positive mononuclear cells. These findings imply that mucins, including MUC-1, may be related to immunoinflammatory reactions in the pathogenesis of RA.

Allograft inflammatory factor-1 is overexpressed and induces fibroblast chemotaxis in the skin of sclerodermatous GVHD in a murine model.

Allograft inflammatory factor (AIF)-1 has been identified in chronic rejection of rat cardiac allografts and is thought to be involved in the immune response. We previously showed that AIF-1 was strongly expressed in synovial tissues in rheumatoid arthritis and that rAIF-1 increased the IL-6 production of synoviocytes and peripheral blood mononuclear cells. Recently, the expression of AIF-1 has been reported in systemic sclerosis (SSc) tissues, whose clinical features and histopathology are similar to those of chronic graft-vs-host disease (GVHD). To clarify the pathogenic mechanism of fibrosis, we examined the expression and function of AIF in sclerodermatous (Scl) GVHD mice. We demonstrated that immunoreactive AIF-1 and IL-6 were significantly expressed in infiltrating mononuclear cells and fibroblasts in thickened skin of Scl GVHD mice compared with control. The immunohistochemical findings were confirmed by Western blot analysis. Wound healing assay also revealed that rAIF-1 increased the migration of normal human dermal fibroblasts (NHDF) directly, but cell growth assay did not show that rAIF-1 increased the proliferation of them. These findings suggest that AIF-1, which can induce the migration of fibroblasts and the production of IL-6 in affected skin tissues, is an important molecule promoting fibrosis in GVHD. Although the biological function of AIF-1 has not been completely elucidated, AIF-1 can induce IL-6 secretion on mononuclear cells and fibroblast chemotaxis. AIF-1 may accordingly provide an attractive new target for antifibrotic therapy in SSc as well as Scl GVHD.

Contribution of rheumatoid arthritis disease activity and disability to rheumatoid cachexia.

This cross-sectional study was done to show how nutritional indices influence each other and the contributions made by inflammation to the development of rheumatoid cachexia. We studied 295 female patients with rheumatoid arthritis (RA). We chose five nutritional indices: body mass index (BMI), arm muscle area (AMA), triceps skinfold thickness (TSF), which were obtained via anthropometric measurements, and serum albumin and cholesterol. Clinical indicators of RA included disease duration, C-reactive protein (CRP) and Disease Activity Score 28 (DAS28). We performed a bivariate correlation test between the nutritional indices and multiple regression analysis for each nutritional index. Mean AMA was low, 87.3% of the normal value, whereas TSF was not different. Muscle protein expressed by AMA decreased according to RA duration, whereas visceral protein indicated by serum albumin decreased with an increase in RA activity. The continuation of inflammation appears to be essential for a decrease in muscle protein in rheumatoid cachexia. DAS28 showed a positive contribution to BMI in the regression model, and the increase in RA disease activity causes an increase in BMI via an accumulation of tissue fat.