Identification of gut dysbiosis in axial spondyloarthritis patients and improvement of experimental ankylosing spondyloarthritis by microbiome-derived butyrate with immune-modulating function

IntroductionDysbiosis is an environmental factor that affects the induction of axial spondyloarthritis (axSpA) pathogenesis. In the present study, we investigated differences in the gut microbiota of patients with axSpA and revealed an association between specific gut microbiota and their metabolites, and SpA pathogenesis.MethodUsing 16S rRNA sequencing data derived from feces samples of 33 axSpA patients and 20 healthy controls (HCs), we examined the compositions of their gut microbiomes.ResultsAs a result, axSpA patients were found to have decreased α-diversity compared to HCs, indicating that axSpA patients have less diverse microbiomes. In particular, at the species level, Bacteroides and Streptococcus were more abundant in axSpA patients than in HCs, whereas Faecalibacterium (F). prausnitzii, a butyrate-producing bacteria, was more abundant in HCs. Thus, we decided to investigate whether F. prausnitzii was associated with health conditions by inoculating F. prausnitzii (0.1, 1, and 10 μg/mL) or by administrating butyrate (0.5 mM) into CD4+ T cells derived from axSpA patients. The levels of IL-17A and IL-10 in the CD4+ T cell culture media were then measured. We also assessed osteoclast formation by administrating butyrate to the axSpA-derived peripheral blood mononuclear cells. The CD4+ IL-17A+ T cell differentiation, IL-17A levels were decreased, whereas IL-10 was increased by F. prausnitzii inoculation. Butyrate reduced CD4+ IL-17A+ T cell differentiation and osteoclastogenesis.DiscussionWe found that CD4+ IL-17A+ T cell polarization was reduced, when F. prausnitzii or butyrate were introduced into curdlan-induced SpA mice or CD4+ T cells of axSpA patient. Consistently, butyrate treatment was associated with the reduction of arthritis scores and inflammation levels in SpA mice. Taken together, we concluded that the reduced abundance of butyrate-producing microbes, particularly F. prausnitzii, may be associated with axSpA pathogenesis

Rheumatoid Arthritis: Pathogenic Roles of Diverse Immune Cells

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease associated with synovial tissue proliferation, pannus formation, cartilage destruction, and systemic complications. Currently, advanced understandings of the pathologic mechanisms of autoreactive CD4+ T cells, B cells, macrophages, inflammatory cytokines, chemokines, and autoantibodies that cause RA have been achieved, despite the fact that much remains to be elucidated. This review provides an updated pathogenesis of RA which will unveil novel therapeutic targets

Supplemental Material - Predictors for future development of systemic lupus erythematosus in Korean Sjögren’s syndrome patients

Supplemental Material for Predictors for future development of systemic lupus erythematosus in Korean Sjögren’s syndrome patients by Bong-Woo Lee, Eui-Jong Kwon, Youngjae Park, Jennifer Jooha Lee, Ji Hyeon Ju, Sung-Hwan Park, and Seung-Ki Kwok in Lupus.</p

Radiographic Structural Damage Is Worse in the Dominant than the Non-Dominant Hand in Individuals with Early Rheumatoid Arthritis

<div><p>Objective</p><p>The relationship between mechanical stress and radiographic progression in rheumatoid arthritis (RA) is unclear. The assumption is that mechanical stress is greater in the dominant hand. Therefore, the aim of the present study was to compare the presence and progression of erosions and joint space narrowing (JSN) in the dominant and non-dominant hand.</p><p>Methods</p><p>Data from 194 patients recently diagnosed with seropositive RA, and with hand radiographs taken at the time of diagnosis and at 2-year follow-up, were analyzed retrospectively. Radiographs were scored using the van der Heijde-modified Sharp Score (HSS) method. Each joint group within each hand was rated separately by two independent examiners in a double-blinded manner.</p><p>Results</p><p>One hundred and ninety-four patients were enrolled (80% female, 88% positive rheumatoid factor, 92% positive anti-citrullinated protein antibody, and 95.4% right-handed). The baseline, follow-up erosion and JSN HSS were significantly higher in the dominant hand than in the non-dominant hand. The annual rate of radiographic progression was also higher in the dominant hand. The erosive progression in the wrist joints varied significantly according to handedness, but the erosion in the proximal interphalangeal joints and metacarpophalangeal joints was similar in both hands. The radiographic progression was associated with the dominant hand, an abnormal baseline C-reactive protein level, and joint damage at baseline. There was no significant difference in bone mineral density between the right and left hands.</p><p>Conclusion</p><p>Radiological damage was worse and progressed faster in the dominant hand, suggesting that mechanical stress is associated with radiographic joint damage in early and active RA.</p></div

Baseline characteristics of the 194 patients with newly-diagnosed rheumatoid arthritis.

<p>DMARDs, disease-modifying anti-rheumatic drugs</p><p>^a Plus-minus values represent the mean ± SE.</p><p>^b Reference range, 0–20 IU/mL.</p><p>^c Reference range, < 7 U/mL.</p><p>^d Reference range, 0.01–0.47 IU/mL.</p><p>Baseline characteristics of the 194 patients with newly-diagnosed rheumatoid arthritis.</p

Annual changes in the van der Heijde modified Sharp score between the dominant and non-dominant hand.

<p>JSN, joint space narrowing; MCPs, metacarpal joints; PIPs, proximal interphalangeal joints; SE, Standard error</p><p>Annual changes in the van der Heijde modified Sharp score between the dominant and non-dominant hand.</p

Hand total, erosion and joint space narrowing (JSN) van der Heijde modified Sharp scores (HSS) at baseline and at 2-year follow-up, time-to-radiographic progression and annual progression according to handedness.

<p>Radiographic progression was defined as a change in the erosive or JSN HSS ≥ 1.5 and a total HSS ≥ 3 in both hands during the follow-up period. (A) Baseline and follow-up total HSS were significantly higher in the dominant hand than in the non-dominant hand. The Log-rank test identified a significant difference in overall progression between the dominant and non-dominant hand (<i>P</i> = 0.041). (B and C) Baseline and follow-up erosion and JSN score were significantly higher in the dominant hand than in the non-dominant hand. The overall erosion and JSN progression rates were 5.7% and 7.5% respectively, during the 2-year follow period. (D) Annual progression of erosion, JSN, and both, were more rapid in the dominant hand.</p

Comparison of the mean mid-bone-to-periarticular BMD ratio in the right and left hands.

<p>BMD, bone mineral density; IQR, interquartile range; PIPs, proximal interphalangeal joints.</p><p>Comparison of the mean mid-bone-to-periarticular BMD ratio in the right and left hands.</p

DataSheet_1_Identification of gut dysbiosis in axial spondyloarthritis patients and improvement of experimental ankylosing spondyloarthritis by microbiome-derived butyrate with immune-modulating function.docx

IntroductionDysbiosis is an environmental factor that affects the induction of axial spondyloarthritis (axSpA) pathogenesis. In the present study, we investigated differences in the gut microbiota of patients with axSpA and revealed an association between specific gut microbiota and their metabolites, and SpA pathogenesis.MethodUsing 16S rRNA sequencing data derived from feces samples of 33 axSpA patients and 20 healthy controls (HCs), we examined the compositions of their gut microbiomes.ResultsAs a result, axSpA patients were found to have decreased α-diversity compared to HCs, indicating that axSpA patients have less diverse microbiomes. In particular, at the species level, Bacteroides and Streptococcus were more abundant in axSpA patients than in HCs, whereas Faecalibacterium (F). prausnitzii, a butyrate-producing bacteria, was more abundant in HCs. Thus, we decided to investigate whether F. prausnitzii was associated with health conditions by inoculating F. prausnitzii (0.1, 1, and 10 μg/mL) or by administrating butyrate (0.5 mM) into CD4+ T cells derived from axSpA patients. The levels of IL-17A and IL-10 in the CD4+ T cell culture media were then measured. We also assessed osteoclast formation by administrating butyrate to the axSpA-derived peripheral blood mononuclear cells. The CD4+ IL-17A+ T cell differentiation, IL-17A levels were decreased, whereas IL-10 was increased by F. prausnitzii inoculation. Butyrate reduced CD4+ IL-17A+ T cell differentiation and osteoclastogenesis.DiscussionWe found that CD4+ IL-17A+ T cell polarization was reduced, when F. prausnitzii or butyrate were introduced into curdlan-induced SpA mice or CD4+ T cells of axSpA patient. Consistently, butyrate treatment was associated with the reduction of arthritis scores and inflammation levels in SpA mice. Taken together, we concluded that the reduced abundance of butyrate-producing microbes, particularly F. prausnitzii, may be associated with axSpA pathogenesis.</p