Dataset Information

Autoantibody profile in sarcoidosis, analysis from the GRADS sarcoidosis cohort.

ABSTRACT:

Background

Sarcoidosis, a multi-systemic granulomatous disease, is a predominantly T-cell disease but evidence for a role for humoral immunity in disease pathogenesis is growing. Utilizing samples from the Genomic Research in Alpha-1 anti-trypsin Deficiency and Sarcoidosis (GRADS) study, we examined the prevalence of autoantibodies in sarcoidosis patients with pulmonary-only and extra-pulmonary organ involvement compared to normal controls.

Study design and methods

We analyzed serum samples from sarcoidosis patients who participated in the GRADS study utilizing an autoantigen microarray platform for both IgM and IgG antibodies. The cohort included sarcoidosis patients with pulmonary-only disease (POS, n = 106), sarcoidosis patients with extra-pulmonary disease (EPS, n = 120) and a normal control cohort (NC, n = 101). Organ involvement was assessed following a standardized format across all GRADS participating centers.

Results

Sarcoidosis patients overall had increased levels of IgM and IgG autoantibodies compared to normal controls. In addition, several autoantibodies were elevated in the POS and EPS cohorts compared to the NC cohort. Differences in autoantibody levels were also noted between the POS and the EPS cohorts. When comparing organ involvement with sarcoidosis, bone, spleen and ear, nose and throat involvement had higher IgM expression than other organs.

Conclusion

Sarcoidosis patients have elevated IgM and IgG autoantibody levels compared to normal controls. In addition, individuals with pulmonary as well as additional organ involvement had higher IgM expression. Further research is needed focusing on specific organ-autoantibody pairs and role of autoantibodies in disease pathogenesis.

SUBMITTER: Khassawneh B

PROVIDER: S-EPMC9584415 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Autoantibody profile in sarcoidosis, analysis from the GRADS sarcoidosis cohort.

Khassawneh Basheer B Zhu Chengsong C Barkes Briana B Vestal Brian B Shrock Sarah S Gillespie May M Pacheco Karin K Deane Kevin D KD Maier Lisa A LA Li Quan-Zhen QZ Hamzeh Nabeel N

PloS one 20221020 10

<h4>Background</h4>Sarcoidosis, a multi-systemic granulomatous disease, is a predominantly T-cell disease but evidence for a role for humoral immunity in disease pathogenesis is growing. Utilizing samples from the Genomic Research in Alpha-1 anti-trypsin Deficiency and Sarcoidosis (GRADS) study, we examined the prevalence of autoantibodies in sarcoidosis patients with pulmonary-only and extra-pulmonary organ involvement compared to normal controls.<h4>Study design and methods</h4>We analyzed ser ...[more]

PMID: 36264970

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Project description:BACKGROUND:Sarcoidosis is characterised by up-regulation of cytokines and chemokine ligands/receptors and proteolytic enzymes. This pro-inflammatory profile is regulated post-transcriptionally by RNA-binding proteins (RBPs). We investigated in vivo expression of six RBPs (AUF1, HuR, NCL, TIA, TIAR, PCBP2) and two inhibitors of proteolytic enzymes (RECK, PTEN) in pulmonary sarcoidosis and compared it to the expression in four control groups of healthy individuals and patients with other respiratory diseases: chronic obstructive pulmonary disease (COPD), asthma and idiopathic interstitial pneumonias (IIPs). METHODS:RT-PCR was used to quantify the mRNAs in bronchoalveolar (BA) cells obtained from 50 sarcoidosis patients, 23 healthy controls, 30 COPD, 19 asthmatic and 19 IIPs patients. Flow cytometry was used to assess intracellular protein expression of AUF1 and HuR in peripheral blood T lymphocytes (PBTLs) obtained from 9 sarcoidosis patients and 6 healthy controls. RESULTS:Taking the stringent conditions for multiple comparisons into consideration, we consistently observed in the primary analysis including all patients regardless of smoking status as well as in the subsequent sub-analysis limited for never smokers that the BA mRNA expression of AUF1 (p<0.001), TIA (p<0.001), NCL (p<0.01) and RECK (p<0.05) was decreased in sarcoidosis compared to healthy controls. TIA mRNA was also decreased in sarcoidosis compared to both obstructive pulmonary diseases (COPD and asthma; p<0.001) but not compared to IIPs. There were several positive correlations between RECK mRNA and RBP mRNAs in BA cells. Also sarcoidosis CD3+, CD4+ and CD8+ PBTLs displayed lower mean fluorescence intensity of AUF1 (p?0.02) and HuR (p?0.03) proteins than control healthy PBTLs. CONCLUSION:mRNA expressions of three RBPs (AUF1, TIA and NCL) and their potential target mRNA encoding RECK in BA cells and additionally protein expression of AUF1 and HuR in PBTLs were down-regulated in our sarcoidosis patients compared to healthy individuals. Its significance, e.g. for stability of mRNAs encoding pro-inflammatory factors, should be further explored in sarcoidosis.

Dataset Information

Autoantibody profile in sarcoidosis, analysis from the GRADS sarcoidosis cohort.

Background

Study design and methods

Results

Conclusion

Publications

Autoantibody profile in sarcoidosis, analysis from the GRADS sarcoidosis cohort.

Similar Datasets

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