Clinical relevance of autoantibodies targeting peptidylarginine deiminases 2 and 4 in rheumatoid arthritis / 中华检验医学杂志

Objective:To evaluate the clinical performance of anti-peptidylarginine deiminase 2 (PAD2) and anti-PAD4 antibodies combined testing in a Chinese rheumatoid arthritis (RA) cohort.Methods:A total of 148 RA inpatients and 35 patients with non-RA arthritis as controls (DC) were recruited from November, 2018 to November, 2019 in Peking University People′s Hospital. In addition, a total of 44 healthy controls (HC) who went to Peking University People′s Hospital for annual physical examination were collected from June 2019 to July 2019. The α-PAD2 and α-PAD4 level in clinical specimens were determined by ELISA. Statistical analysis was performed by the Mann-Whitney U test, the Kruskal-Wallis (KW) test, the χ 2 test or the Fisher′s Exact Test, as necessary. Correlation analysis were performed by logistic regression. Results:α-PAD2 and α-PAD4 were present in 26.4% (39/148) and 20.9% (31/148) patients with RA, 5.7% (2/35) and 5.7% DC (2/35) and 4.5% (2/44) and 2.3% HC (2/44), respectively. α-PAD4-positive RA patients displayed significantly longer disease duration compared to α-PAD4-negative RA patients (17.3±13.2 years vs 8.6±10.2 years, P<0.001). α-PAD4-positive RA patients showed a significantly higher incidence of interstitial lung disease (ILD) compared to those without α-PAD4 (54.8% vs 25.6%, P=0.002). No associations between α-PAD2 and ILD were found ( OR: 0.797, P=0.579). In contrast, significant associations between α-PAD4 and ILD were found ( OR: 3.521, P=0.002). In seropositive RA, α-PAD4 displayed a weak correlation with ILD ( OR: 2.324, P=0.046), but this association was greatly enhanced when combined with α-PAD2 [anti-PAD2 (-)] ( OR: 4.059, P=0.007). Conclusions:The findings delineate the clinical relevance of α-PAD2 and α-PAD4 in RA and suggest that the combined testing for α-PAD2 and α-PAD4 may provide additional diagnostic value to the current clinically available assays in RA, in particular in identifying patients at risk of RA-ILD.

Evaluation of peptidylarginine deiminase 4 and PADI4 polymorphisms in sepsis-induced acute kidney injury

SUMMARY BACKGROUND: The aim of this study is to evaluate the peptidylarginine deiminase 4 (PAD 4) concentration and PADI4 polymorphisms as predictors of acute kidney injury (AKI) development, the need for renal replacement therapy (RRT), and mortality in patients with septic shock. METHODS: We included all individuals aged ≥ 18 years, with a diagnosis of septic shock at ICU admission. Blood samples were taken within the first 24 hours of the patient's admission to determine serum PAD4 concentration and its PADI4 polymorphism (rs11203367) and (rs874881). Patients were monitored during their ICU stay and the development of SAKI was evaluated. Among the patients in whom SAKI developed, mortality and the need for RRT were also evaluated. RESULTS: There were 99 patients, 51.5% of whom developed SAKI and of these, 21.5% needed RRT and 80% died in the ICU. There was no difference between PAD4 concentration (p = 0.116) and its polymorphisms rs11203367 (p = 0.910) and rs874881 (p = 0.769) in patients in whom SAKI did or did not develop. However, PAD4 had a positive correlation with plasma urea concentration (r = 0.269 and p = 0.007) and creatinine (r = 0.284 and p = 0.004). The PAD4 concentration and PADI4 polymorphisms were also not associated with RRT and with mortality in patients with SAKI. CONCLUSION: PAD4 concentration and its polymorphisms were not associated with SAKI development, the need for RRT, or mortality in patients with septic shock. However, PAD4 concentrations were associated with creatinine and urea levels in these patients.

RESUMO OBJETIVO: Avaliar a concentração da peptidilarginina deiminase 4 (PAD4) e os polimorfismos de PADI4, como preditores de desenvolvimento de lesão renal aguda, necessidade de terapia renal substitutiva (TRS) e mortalidade em pacientes com choque séptico. MÉTODOS: Foram incluídos indivíduos com idade ≥18 anos, com diagnóstico de choque séptico na admissão na Unidade de Terapia Intensiva (UTI). Amostras de sangue foram coletadas nas primeiras 24 horas após a admissão do paciente para determinar a concentração sérica de PAD4 e seus polimorfismos PADI4 (rs11203367) e (rs874881). Os pacientes foram acompanhados durante a internação na UTI e tiveram avaliados desenvolvimento da lesão renal aguda séptica (Sepsis-induced acute kidney injury - Saki), necessidade TRS e mortalidade. RESULTADOS: Foram avaliados 99 pacientes; 51,5% desenvolveram Saki e, desses, 21,5% necessitaram de TRS e 80% morreram na UTI. Não houve diferença entre a concentração de PAD4 (p=0,116) e seus polimorfismos rs11203367 (p=0,910) e rs874881 (p=0,769) entre os pacientes. No entanto, o PAD4 apresentou correlação positiva com a concentração plasmática de ureia (r=0,269; p=0,007) e creatinina (r=0,284; p=0,004). A concentração de PAD4 e os polimorfismos da PADI4 também não foram associados à TRS e à mortalidade em pacientes com Saki. CONCLUSÕES: A concentração de PAD4 e seus polimorfismos não foram associados ao desenvolvimento de Saki, à necessidade de TRS ou à mortalidade em pacientes com choque séptico. No entanto, as concentrações de PAD4 foram associadas às concentrações de creatinina e ureia nesses pacientes.