Deciphering the association of celiac disease and other comorbidities in patients with rheumatoid arthritis using systems and clinical medicine approaches
Keywords:
Rheumatoid Arthritis, Diabetes Mellitus, Celiac Disease, Immunoglobulin A, Tissue Transglutaminase, Fasting Blood Sugar, Vitamin D3, Personalized TreatmentAbstract
In this study, we decipher the association of celiac disease (CD) and other comorbidities in patients with rheumatoid arthritis (RA) using key clinical risk factors and systems medicine approaches for the differential diagnosis and personalized treatment. In the systems medicine approach, we have used the Ingenuity Pathway Analysis knowledgebase (IPA, Qiagen, USA) to decipher the upstream regulators of the disease, canonical pathways, molecular networks and disease specific pathways commonly shared in RA and CD. Besides, eighty-two RA patients who have satisfied “American College of Rheumatology (ACR)” classification criteria for RA and 20 healthy volunteers were participated. RA patients with CD were identified based on serum levels of immunoglobulin A (IgA) autoantibodies to tissue transglutaminase (tTG-IgA). Besides, clinical parameters such as fasting blood sugar (FBS) and glycosylated hemoglobin A1C (HbA1C) were measured to assess the diabetic state. Clinical parameters such as erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), C-reactive protein (CRP), mean cell volume (MCV), mutated citrullinated vimentin antibodies (anti-MCV), white blood count (WBC), albumin, calcium (Ca2+) and vitamin D3 (VitD3) were analyzed in healthy volunteers, RA, and RA with CD cohorts respectively. Systems medicine analyses showed that both RA and CD strongly associated with diabetes mellitus. Furthermore, clinical analyses indicate that FBS, HbA1C, Anti-MCV, RF, CRP and tTG-IgA concentrations were significantly increased in both RA and RA with CD cohorts than healthy controls. tTG-IgA levels were significantly elevated in RA with CD cohorts compared with RA. On the other hand, anti-MCV levels were significantly increased in RA compared to RA with CD group. Besides, both RA and RA with CD cohorts have significantly reduced levels of VitD3 and Albumin in the serum compared with healthy controls. In conclusion, the RA and RA with CD cohorts have poor glycemic rheostat compared to healthy controls. Higher serum tTG-IgA levels in these cohorts indicate the susceptibility of RA patients to develop CD. The reduction in serum VitD3 levels in both RA and RA with CD cohorts further worsens disease prognosis. The systems medicine and clinical analyses, therefore, showed the potential association of diabetes mellitus (DM) and CD in RA patients. Key words: Rheumatoid Arthritis, Diabetes Mellitus, Celiac Disease, Immunoglobulin A, Tissue Transglutaminase, Fasting Blood Sugar, Vitamin D3, Personalized Treatment.
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