Kaplan–Meier survival curves for patients with interstitial lung disease associated with primary Sjögren’s syndrome.

<p>(a) Survival curve for the total patient population. Five-year survival rate was 87.3%. (b) Comparison of survival curves between the NSIP (n = 22) and UIP (n = 11) patients. Open circles or open squares show censored cases in NSIP group or UIP group, respectively. The prognosis between the two groups was not significantly different (<i>P</i> = 0.93 in log–rank test). UIP: usual interstitial pneumonia; NSIP: nonspecific interstitial pneumonia.</p

Examples of pathological scoring (hematoxylin–eosin, × 100).

<p>Typical images in each grade of fibroblastic foci (straight arrows) [(a): grade 1 and (b): grade 3] and bronchiolar fibrosis [(c): grade 1 and (d): grade 3] were listed.</p

Kaplan-Meier survival curves of all-cause mortality.

<p>Overall cumulative 5-year mortality was 24.4%. (A) Patients with ScAb-ILD (dotted line) had worse survival than those with SSc-ILD (dashed line) (p = 0.011). (B) In patients with ScAb-ILD, those with extensive disease (dashed line) had worse survival than those with limited disease (solid line) (p = 0.015). (C) In patients with SSc-ILD, those with KL-6 ≥ 1000 U/mL (dashed line) had worse survival than those with KL-6 < 1000 U/mL (solid line) (p = 0.049). (D) The survival curves for patients with each type of autoantibody were not significantly different (p = 0.905 for comparison between anti-scleroderma-70 and anti-U1 RNP antibody, p = 0.089 for comparison between anti-scleroderma-70 and anti-centromere antibody, and p = 0.137 for comparison between anti-U1 RNP and anti-centromere antibody).</p

Analysis of factors associated with mortality.

<p>Analysis of factors associated with mortality.</p

Baseline characteristics at the time of diagnosis as interstitial lung disease.

<p>Baseline characteristics at the time of diagnosis as interstitial lung disease.</p

Examples of pathological scoring.

<p>(A-B) Typical imaging in each grade of organizing pneumonia (intra-alveolar polyps) as found in patients with ScAb-ILD (hematoxylin-eosin stain) ([A]: grade 1 and [B]: grade 3). (C-D) Vascular intimal or medial thickening as found in patients SSc-ILD (Elastica van Gieson stain) ([C]: grade 1 and [D] grade 3].</p

Comparison of HRCT and pathological findings between SSc-ILD and ScAb-ILD.

<p>Comparison of HRCT and pathological findings between SSc-ILD and ScAb-ILD.</p

Changes in forced vital capacity (FVC) during follow-up.

<p>(A) SSc-ILD (B) ScAb-ILD (C) Regression lines were calculated by solving the linear mixed-effects model. Baseline FVC (intercept) with ScAb-ILD (mean, 2.574 L [95% CI: 2.313–2.835]) was significantly higher than that with SSc-ILD (mean, 2.191 L [95% CI: 1.974–2.407]) (p = 0.027). The declining slopes of FVC between both groups were not significantly different (SSc-ILD: mean, -0.03979 L year^-1 [95% CI: -0.05449 to -0.02509]; ScAb-ILD: mean, -0.03740 L year^-1 [95% CI: -0.06446 to -0.01034] (p = 0.878).</p

HRCT scans of cyst formation.

<p>(A-B) HRCT scan demonstrates cyst formation (arrowheads) with pulmonary fibrosis, traction bronchiectasis, and architectural distortion in two patients with SSc-ILD. There is no continuity between the cysts and traction bronchiectasis. (C) HRCT scan shows cysts (arrowheads) with opacity separated from the pleura in a patient with MCTD-ILD.</p

<i>Propionibacterium acnes</i>-derived insoluble immune complexes in sinus macrophages of lymph nodes affected by sarcoidosis

<div><p>Background</p><p><i>Propionibacterium acnes</i> is thought to be a causative agent of sarcoidosis. Patients with sarcoidosis have circulating immune complexes. We attempted to detect <i>P</i>. <i>acnes</i>-derived immune complexes in sarcoid lesions.</p><p>Methods</p><p>We evaluated formalin-fixed and paraffin-embedded lymph node samples from 38 sarcoidosis patients and 90 non-sarcoidosis patients (27 patients with necrotizing lymphadenitis, 28 patients with reactive lymphadenitis, 16 patients with colon cancer, 19 patients with gastric cancer) by immunohistochemistry using anti-human immunoglobulins (IgG, IgA, and IgM) and complement (C1q and C3c) antibodies, and a <i>P</i>. <i>acnes</i>-specific monoclonal antibody (PAB antibody) that reacts with the membrane-bound lipoteichoic acid of <i>P</i>. <i>acnes</i>.</p><p>Results</p><p>Small round bodies (SRBs) bound to IgA, IgM, or IgG were detected in sinus macrophages, in 32 (84%), 32 (84%), or 11 (29%) sarcoid samples, respectively, and in 19 (21%), 26 (29%), or no (0%) control samples, respectively. Some of these insoluble immune complexes (IICs) also bound to C1q and C3c. We developed a microwave treatment followed by brief trypsin digestion (MT treatment) to detect PAB-reactive SRBs bound to immunoglobulins (IIC-forming <i>P</i>. <i>acnes</i>). MT treatment revealed abundant IIC-forming <i>P</i>. <i>acnes</i> in most (89%) of the sarcoid samples and sparse distribution in some (20%) of the control samples with lymphadenitis, but no IIC-forming <i>P</i>. <i>acnes</i> was detected in control samples without inflammation. IIC-forming <i>P</i>. <i>acnes</i> were mostly bound to both IgA and IgM. The PAB-reactive antigen and immunoglobulins were both located at the peripheral rim of the IIC-forming <i>P</i>. <i>acnes</i>. Conventional electron microscopy identified many SRBs (0.5–2.0 μm diameter) in sinus macrophages of sarcoid lymph nodes with many IIC-forming <i>P</i>. <i>acnes</i>, some of which were in phagolysosomes with a degraded and lamellar appearance.</p><p>Conclusions</p><p><i>P</i>. <i>acnes</i>-derived IICs in sinus macrophages were frequent and abundant in sarcoid lymph nodes, suggesting a potential etiologic link between sarcoidosis and this commensal bacterium.</p></div