Abstract

Abstract Background The presence of antibodies against cyclic citrullinated proteins (anti-CCP) precede the development of rheumatoid arthritis (RA) and both anti-CCP antibody and RF positivity indicate more severe disease. This characteristic makes Anti-CCP best biomarker candidate for the prevention of debilitating joint disease. Almost 70% of RA patients are positive for anti-CCP IgG, while only 2% of control subjects are positive for anti-CCP. Understanding the origins of anti-CCP is critical in unraveling the etiology of RA, so we further evaluated the association of the other autoimmune tests/biomarkers with Anti-CCP to describe other comorbid autoimmune diseases/syndrome. Methods We conducted a retrospective analysis of patient data from April 18, 2016, to May 29, 2019, in Texas. The study protocol was approved by the ethics review committee and patients consented for sharing their demographics, clinical information and lab values for diagnostic and research purposes. The study population was described by descriptive statistics. Demographic characteristics and laboratory parameters were compared using chi-square tests. We analyzed blood tests/parameters conducted at the clinics and explored their association with the presence of ACCP. logistic regression models were utilized to calculate the odds ratio to delineate the strength of association of different blood parameters with ACCP. IgG anti-CCP was determined according to the manufacturer’s instruction. Results Eleven thousand, four hundred fifty-nine tests were performed on 7,200 patients with a mean age of 52 years (range 0-98). Almost half (54%) of study individuals were females, two-third (63%) were White, (29%) Hispanic and (7%) African American. Four hundred and six patients (3.5%) were positive for AntiCCP3.1. Among those who were positive for AntiCCP3.1, (22%) were Rh factor IgA (RhIgA) positive, (11%) RhIgG positive, and (9%) RhIgM. Univariate logistic regression showed that the female gender was positively associated (OR = 3.19) with ACCP presence while patients older than 50 had a positive gradient of ACCP positivity with each age category. Compared to White, African Americans were more likely (OR = 3.19) and Hispanics were less likely (OR = 0.44) to be associated with AntiCCP positivity. After controlling for age, gender and ethnicity the presence of RhIgM and RhIgA antibodies were positively associated with positive ACCP. (OR = 13.3, OR = 5.2). antiphosphatidylserine IgM and anticardiolipin IgM antibodies were positively associated with ACCP (OR = 2.1, OR = 3.4). Similarly, the presence of antimitochondrial M2 antibodies and anti-topoisomerase antibodies (SCL-70) were very significantly associated with ACCP (OR = 16.1, OR = 37.8). Conclusion The Anti-CCP antibodies are highly specific for the early diagnosis of RA and with early initiation of treatment, progression to irreversible and destructive diseases can be prevented. Association of Anti-CCP antibodies with other autoimmune antibodies highlights the importance of screening RA patients for primary biliary sclerosis and scleroderma. Similarly, a biomarker's strength of interaction with another biomarker helps in the prognostic utility of these test for preventing co-existing diseases. Disclosures M. Ayass: Other; Physician at Ayass Bioscience. K. Zhu: Other; Employee at Ayass Bioscience. S. Naveed: None. L. Mosleh: Other; Employee at Ayass Bioscience. K. Viswanathan: Other; Employee at Ayass Bioscience. G. Nowshad: Other; Employee at Ayass Bioscience.

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