Isolated DLco/VA reduction in systemic sclerosis patients: a new patient subset?

INTRODUCTION: Diffusing capacity for carbon monoxide (DLco) reduction is the first detectable pulmonary functional test (PFT) change in systemic sclerosis (SSc)-related pulmonary complications. reduction in patients without cardiopulmonary alterations has also been observed; a good characterisation of these patients is lacking. The objective of this study is to describe the characteristics of SSc patients with isolated DLco reduction and compare these patients to SSc patients with DLco reduction with a known cause. METHODS: SSc patients with DLco < 80% predicted were included and classified into cases (isolated DLco reduction) and controls (DLco reduction in the presence of known pulmonary pathology). SSc clinico-serological data, PFT and echocardiography features were collected and analysed. RESULTS: From a total SSc cohort of 115 patients, 75 patients were included: 20 cases (26.7%) and 55 controls (73.3%). Cases were predominantly limited skin subset (90% vs 60%, p < 0.001), were anti-centromere antibody (ACA)-positive (95% vs 40%, p < 0.001) and had an infrequent oesophageal involvement (45% vs 74%; p = 0.016). The mean DLco reduction of cases was mild (65.60% ± 10.56). Only 1 out of 20 patients had normal DLco/VA values, and tricuspid regurgitation was more frequent (85% vs 53.8%, p = 0.014). CONCLUSION: There is a subgroup of SSc patients with mild isolated DLco and DLco/VA reduction, predominantly limited SSc with ACA seropositivity, which could identify a particular SSc subset. We hypothesise that isolated DLco/VA reduction could indicate a pulmonary vascular involvement. Nevertheless, a close follow-up is mandatory, as a pre-PAH situation cannot be excluded.

The functional polymorphism 844 A>G in FcαRI (CD89) does not contribute to systemic sclerosis or rheumatoid arthritis susceptibility.

OBJECTIVE: To investigate the role of the Fc(α)RI 844 A>G functional polymorphism in the genetic predisposition to rheumatoid arthritis (RA) and systemic sclerosis (SSc) susceptibility. METHODS: The study population was composed of 1401 patients with SSc, 642 patients with RA, and 1317 healthy controls. The Fc(α)RI (CD89) single-nucleotide polymorphism rs16986050 was genotyped by pyrosequencing. RESULTS: We observed no significant deviation of the genotype and allele frequencies in RA and SSc compared to controls. A metaanalysis and a recessive and dominant model yielded similar negative results. CONCLUSION: Our data show that the Fc(α)RI 844 A>G polymorphism is not associated with SSc or RA susceptibility.

Functional variants of Fc gamma receptor (FCGR2A) and FCGR3A are not associated with susceptibility to systemic sclerosis in a large European Study (EUSTAR).

OBJECTIVE: To investigate the possible role of FCGR2A 519A>G and FCGR3A 559A>C functional polymorphisms in the genetic predisposition to susceptibility to systemic sclerosis (SSc) or clinical phenotype. METHODS: A total of 1566 patients with SSc and 2271 geographically matched controls were included in our study. We analyzed the genotype and allele frequencies of the FCGR2A 519A>G and FCGR3A 559A>C functional variants in 6 independent European cohorts of white patients with SSc, and white controls. The cohorts comprised 165 Dutch patients with SSc and 1326 controls, 236 Spanish patients with SSc and 257 controls, 267 German patients with SSc and 270 controls, 202 Swedish patients with SSc and 261 controls, 416 Italian patients with SSc and 157 controls, and additionally 280 English patients with SSc. Genotyping was performed using Taqman 5' allelic discrimination assay. The study reached a 99% power to detect the effect of a polymorphism at an OR of 1.3. RESULTS: Neither FCGR2A 519A>G nor FCGR3A 559A>C was significantly associated with susceptibility to SSc. We did not find an association with specific disease phenotypes, limited or diffuse cutaneous involvement, autoantibody profiles, or pulmonary involvement. CONCLUSION: Our study strongly suggests the lack of a role for the FCGR2A 519A>G and FCGR3A 559A>C polymorphisms in SSc susceptibility or clinical phenotype in 6 independent European cohorts.