Berti, Alvise

ObjectiveTo evaluate circulating cytokine profiles in patients with antineutrophil cytoplasmic antibody–associated vasculitis (AAV), classified by antineutrophil cytoplasmic antibody (ANCA) specificity (proteinase 3 ANCA [PR3‐ANCA] versus myeloperoxidase ANCA [MPO‐ANCA]) or by clinical diagnosis (granulomatosis with polyangiitis [GPA] versus microscopic polyangiitis [MPA]).MethodsA panel of 29 cytokines was tested in 186 patients with active AAV at inclusion into the Rituximab in AAV trial. Cytokine concentrations were compared between groups within each classification system. Multivariable analyses adjusted for age, sex, and renal insufficiency were performed, with each biomarker as a dependent variable and ANCA specificity and clinical diagnosis as explanatory variables of interest.ResultsLevels of 9 circulating cytokines (interleukin‐6 [IL‐6], granulocyte–macrophage colony‐stimulating factor [GM‐CSF], IL‐15, IL‐18, CXCL8/IL‐8, CCL‐17/thymus and activation–regulated chemokine [TARC], IL‐18 binding protein [IL‐18 BP], soluble IL‐2 receptor α [sIL‐2Rα], and nerve growth factor β [NGFβ]) were significantly higher in PR3‐AAV than MPO‐AAV, 4 cytokines (sIL6R, soluble tumor necrosis factor receptor type II [sTNFRII], neutrophil gelatinase–associated lipocalin [NGAL], and soluble intercellular adhesion molecule 1 [sICAM‐1]) were higher in MPO‐AAV than in PR3‐AAV, 6 cytokines (IL‐6, GM‐CSF, IL‐15, IL‐18, sIL‐2Rα, and NGFβ) were higher in GPA than in MPA, and 3 cytokines (osteopontin, sTNFRII, and NGAL) were higher in MPA than in GPA (all P < 0.05). For nearly all cytokines, the difference between PR3‐AAV and MPO‐AAV was larger than that between GPA and MPA. The multivariate analysis showed that 8 cytokines (IL‐15, IL‐8, IL‐18 BP, NGF‐β, sICAM‐1, TARC, osteopontin, and kidney injury molecule 1 (P < 0.05) distinguished patients with AAV better (lower P values and larger effect sizes) when grouped by ANCA specificity than by clinical diagnosis.ConclusionDistinct cytokine profiles were identified for PR3‐AAV versus MPO‐AAV and for GPA versus MPA. Differences in these circulating immune mediators are more strongly associated with ANCA specificity than with clinical diagnosis, suggesting that heterogeneity in the AAV subtypes extends beyond clinical phenotypes.

Objective To determine rates and primary discharge diagnoses of hospitalisation in a cohort of patients with incident primary Sjögren’s syndrome (pSS) compared with the general population. Methods This was a retrospective population-based cohort study focused on Olmsted County, Minnesota. The pSS cohort consisted of patients with incident pSS in the 1976–2015 period and was compared with a cohort of individuals without pSS matched 3:1 for age, sex and calendar year, randomly selected from the same population. Hospitalisations in 1995–2016 were examined. Discharge diagnoses were categorised using the Clinical Classifications Software for International Classification of Diseases, 9th revision, Clinical Modification. Results A total of 385 hospitalisations occurred in the 160 patients with pSS during 1592 person-years of follow-up. Among 466 comparators, there were 899 hospitalisations during 4660 person-years of follow-up, resulting in a significantly higher rate of hospitalisations in patients with pSS (rate ratio (RR): 1.25, 95% CI: 1.11 to 1.41). Rates of hospitalisation were increased among patients with pSS for endocrine, nutritional and metabolic diseases and immunity disorders (RR 1.82, 95% CI 1.08 to 2.98), diseases of the musculoskeletal system and connective tissue (RR 1.49, 95% CI 1.05 to 2.05) and for injuries and poisoning (RR 1.46, 95% CI 1.01 to 2.06). While not significantly increased overall, hospitalisations for diseases of the circulatory system were significantly increased in patients with pSS aged ≥75 years (RR 1.54, 95% CI 1.11 to 2.11). Conclusions Patients with pSS experienced higher rates of hospitalisation than the general population. Hospitalisations for endocrine/metabolic disorders, diseases of the circulatory system, diseases of the musculoskeletal system and connective tissue disorders, and injuries were more common among patients with pSS than comparators.

ObjectiveTo estimate the annual incidence, prevalence, and mortality of antineutrophil cytoplasmic autoantibody (ANCA)–associated vasculitis (AAV) and its subsets, granulomatosis with polyangiitis (Wegener's) (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (Churg‐Strauss) (EGPA), in a US‐based adult population.MethodsAll medical records of patients with a diagnosis of, or suspicion of having, AAV in Olmsted County, Minnesota from January 1, 1996 to December 31, 2015 were reviewed. AAV incidence rates were age‐ and sex‐adjusted to the 2010 US white population. Age‐ and sex‐adjusted prevalence of AAV was calculated on January 1, 2015. Survival rates observed in the study cohort were compared with expected rates in the Minnesota population.ResultsOf the 58 incident cases of AAV in Olmsted County during the study period, 23 (40%) were cases of GPA, 28 (48%) were cases of MPA, and 7 (12%) were cases of EGPA. Overall, 28 (48%) of the patients with AAV were women and 57 (98%) were white. The mean ± SD age at diagnosis was 61.1 ± 16.5 years. Thirty‐four patients (61%) had myeloperoxidase (MPO)–ANCAs, and 17 (30%) were positive for proteinase 3 (PR3)–ANCAs; 5 (9%) were ANCA‐negative. The annual incidence of AAV was 3.3 per 100,000 population (95% confidence interval [95% CI] 2.4–4.1). The incidence rates of GPA, MPA, and EGPA were 1.3 (95% CI 0.8–1.8), 1.6 (95% CI 1.0–2.2), and 0.4 (95% CI 0.1–0.6), respectively. The overall prevalence of AAV was 42.1 per 100,000 (95% CI 29.6–54.6). The mortality rate among AAV patients overall, and among patients with EGPA, those with MPA, and those with MPO‐ANCAs, was increased in comparison to the Minnesota general population (each P < 0.05), whereas mortality rates among patients with GPA, those with PR3‐ANCAs, and ANCA‐negative patients did not differ from that in the general population.ConclusionThe annual incidence of AAV in Olmsted County, Minnesota over the 20 years of the study was 3.3 per 100,000, with a prevalence of 42.1 per 100,000, which is substantially higher than the rates reported in other areas worldwide. The incidence of GPA was similar to that of MPA. Patients with MPA and those with EGPA, but not patients with GPA, experienced higher rates of mortality than that in the Minnesota general population. MPO‐ANCAs were a marker of poor survival in this population of patients with AAV.