Impact of etiological factors on citrullination markers and susceptibility of PADI4 allele for CHIKV induced rheumatoid arthritis among South Indian Tamil RA cases

Venkatraman Malini; Narayanasamy Shettu; Subbiah Murugesan; Venkatraman Malini; Narayanasamy Shettu; Subbiah Murugesan

doi:10.3934/Allergy.2022012

AIMS Allergy and Immunology

2022, Volume 6, Issue 3: 153-169. doi: 10.3934/Allergy.2022012

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Impact of etiological factors on citrullination markers and susceptibility of PADI4 allele for CHIKV induced rheumatoid arthritis among South Indian Tamil RA cases

1.
PG and Research Department of Zoology, Pachaiyappa's College, University of Madras, Chennai, Tamil Nadu, India
2.
Unit of Algal Biotechnology and Bionanotechnology, PG and Research Department of Botany, Pachaiyappa's College, University of Madras, Chennai, Tamil Nadu, India

Received: 01 April 2022 Revised: 22 August 2022 Accepted: 01 September 2022 Published: 13 September 2022

Rheumatoid arthritis (RA) is a multifactorial disease which can be triggered by gene-environment interactions. Numerous risk factors have been acknowledged in varied ethnicities, but their generalizability is vague. Hence, proposed to identify impact of etiology on citrullination and how both interact with peptidyl arginine deiminase 4 (PADI4) polymorphism in RA onset among South Indian Tamil RA cases. Studied 207 RA cases and 186 healthy controls for C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP), anti-Sa (citrullinated vimentin), anti-citrullinated α-enolase peptide-1 (CEP-1) and diseases activity score-28 (DAS-28). Past exposure to studied etiological risk factors obtained through questionnaire. Family history of RA (FHRA), surgery/injury and chikungunya virus (CHIKV) infection significantly contributed to RA (p < 0.05) particularly CHIKV (OR = 6.66, 95% CI 3.92–11.32, p = 0.001). Strikingly, 67.1% of surgery/injury and 80% of CHIKV exposed patients had RA onset within a year. RA cases with tooth decay had impact on RF, anti-CCP, anti-Sa freequeny and anti-CEP-1 level (p < 0.05).Since CHIKV infected cases showed significant anti-Sa (p = 0.04) level and frequency (p = 0.01), they were genotyped for polymorphism in PADI4_92 (rs874881), 104 (rs1748033) and 94 (rs2240340) by Sanger's sequencing which demonstrated that PADI4 confers risk (p < 0.05) for the onset of CHIKV induced RA. This is the initial report that CHIKV may contribute to RA development via vimentin citrullination. FHRA, surgery/injury, CHIKV and smoking posed a key RA risk.
- anti-CCP,
- anti-CEP-1,
- anti-Sa,
- CHIKV,
- PADI4,
- RA
Citation: Venkatraman Malini, Narayanasamy Shettu, Subbiah Murugesan. Impact of etiological factors on citrullination markers and susceptibility of PADI4 allele for CHIKV induced rheumatoid arthritis among South Indian Tamil RA cases[J]. AIMS Allergy and Immunology, 2022, 6(3): 153-169. doi: 10.3934/Allergy.2022012

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Abstract

Rheumatoid arthritis (RA) is a multifactorial disease which can be triggered by gene-environment interactions. Numerous risk factors have been acknowledged in varied ethnicities, but their generalizability is vague. Hence, proposed to identify impact of etiology on citrullination and how both interact with peptidyl arginine deiminase 4 (PADI4) polymorphism in RA onset among South Indian Tamil RA cases. Studied 207 RA cases and 186 healthy controls for C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP), anti-Sa (citrullinated vimentin), anti-citrullinated α-enolase peptide-1 (CEP-1) and diseases activity score-28 (DAS-28). Past exposure to studied etiological risk factors obtained through questionnaire. Family history of RA (FHRA), surgery/injury and chikungunya virus (CHIKV) infection significantly contributed to RA (p < 0.05) particularly CHIKV (OR = 6.66, 95% CI 3.92–11.32, p = 0.001). Strikingly, 67.1% of surgery/injury and 80% of CHIKV exposed patients had RA onset within a year. RA cases with tooth decay had impact on RF, anti-CCP, anti-Sa freequeny and anti-CEP-1 level (p < 0.05).Since CHIKV infected cases showed significant anti-Sa (p = 0.04) level and frequency (p = 0.01), they were genotyped for polymorphism in PADI4_92 (rs874881), 104 (rs1748033) and 94 (rs2240340) by Sanger's sequencing which demonstrated that PADI4 confers risk (p < 0.05) for the onset of CHIKV induced RA. This is the initial report that CHIKV may contribute to RA development via vimentin citrullination. FHRA, surgery/injury, CHIKV and smoking posed a key RA risk.

Acknowledgments

Authors are thankful to the HOD of Zoology and the Principal of Pachaiyappa's College for their encouragement and support. The authors are extremely grateful to Director, Hitech Diagnostic Centre, Kilpauk, Chennai-84, for providing technical support and suggestions. We also profusely thank Dr. Shrilekha S, Rheumatology clinic, Chennai for recruiting RA patients for the study.

Conflict of interest

All authors declare no conflicts of interest in this paper.

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