http://informahealthcare.com/mor ISSN 1439-7595 (print), 1439-7609 (online) Mod Rheumatol, 2015; Early Online: 1–7 ! 2015 Japan College of Rheumatology DOI: 10.3109/14397595.2015.1074649 ORIGINAL ARTICLE Anti-C1q antibody in patients with lupus nephritic flare: 18-month follow-up and a nested case-control study Alimohammad Fatemi 1 , Golnaz Samadi 2 , Zahra Sayedbonakdar 1 , and Abbas Smiley 3 1 Department of Rheumatology and 2 Department of Internal Medicine, Isfahan University of Medical Sciences, Isfahan, Iran, and 3 Department of Clinical Epidemiology, Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran Abstract Objectives: A prospective cohort was conducted to investigate the association of anti-C1q antibody and lupus/lupus nephritis (LN) flare. Methods: Sixty-nine consecutive patients with systemic lupus erythematosus were enrolled and followed up for 18 months. Anti-C1q was recorded at the first visit and at the time of flare. For patients with flare, age and sex matched SLE patients were considered as the control group (nested case-control study). The predictability of anti-C1q and other laboratory indices for LN flare during the 18-month follow-up was calculated. Results: Fourteen out of sixty-nine (20%) had lupus flare. Fourteen patients were chosen as controls. Nine cases and three controls had positive anti-C1q at the first visit (p ¼ 0.0001). Twenty-six (38%) and 43 (62%) patients had positive and negative anti-C1q antibody at the first visit, respectively, of whom 9 (34.5%) and 3 (7%) patients developed LN flare in the next 18 months (p ¼ 0.003). Anti-C1q and 24-hour urine protein were found as the main predictors of LN flare. The positive and negative predictive values of anti-C1q for LN flare were 35% and 93%, respectively. Predictive values of positive anti-C1q/low C3 together were 60% and 96%, respectively. Conclusion: The combination of positive anti-C1q/low C3 had the highest reasonable predictive values for LN flare. Keywords Anti-C1q, Flare, Lupus nephritis, Systemic lupus erythematosus History Received 2 May 2015 Accepted 15 July 2015 Published online 7 September 2015 Introduction Given that about 180 different autoantibodies were found in systemic lupus erythematosus (SLE), Yaniv et al. likened it to a volcanic explosion [1]. The huge pool of different autoantibodies in SLE might explain the wide spectrum of clinical manifestations of the disease [2]. Antibodies against the first part of classic complement pathway (anti-C1q) were discovered three decades ago [3]. Although anti-C1q antibody was found primarily in the sera of the patients with SLE, it could be identified in healthy individuals [4], infectious diseases [5] and other rheumatic diseases such as rheumatoid arthritis, scleroderma, vasculitis and Sjogren’s syndrome too [6]. The concept of the association of anti- C1q antibody and SLE disease activity, especially lupus nephritis (LN) was the issue of concern in the recent years [6–13]. The pathogenic mechanism of anti-C1q antibody has been related to the ‘‘waste-disposal’’ hypothesis [14,15]. Based on this theory, the defective clearance of apoptotic cells in patients with SLE leads to expression of autoantigens to immune system and the consequent production of autoantibodies against them. After C1q binding to apoptotic cells, a conformational change occurs in its molecule that induces immune system response resulting in the production of anti-C1q [16,17]. These autoantibodies can augment the complement-mediated tissue injury [16]. Given the more accessibility of apoptotic cells in kidney tissue than in other organs of SLE patients, the more correlation between anti-C1q antibodies and LN might be elucidated [17]. The aim of the current prospective research was to determine the predictive value of anti-C1q antibody and its combination with other laboratory measurements for lupus/LN flare. Patients and methods Patients Sixty-nine consecutive patients were enrolled in this follow-up study. All patients had registered profiles at Lupus Clinic affiliated with Isfahan University of Medical Sciences. They fulfilled four or more of updated 1997 criteria of American College of Rheumatology (ACR) [18]. All participants signed the informed consent. The Regional Ethics Committee approved the study protocol. Patients’ assessment and follow-up Patients were followed-up for 18 months. Demographic charac- teristics were recorded. Standard medical history was taken. Clinical and laboratory findings were assessed at baseline and by the end of study by one rheumatologist. The patients were asked to come back every 1–4 months according to the physician’s judgment. But, in case of symptoms aggravation or new-onset symptoms, they were instructed to return for an earlier visit. Physical examination and laboratory evaluations, except anti-C1q, were repeated in each visit. Anti-C1q was measured at the first and Correspondence to: Alimohammad Fatemi, Department of Rheumatology, Alzahra Hopsital, Isfahan University of Medical Sciences, Isfahan, Iran. Tel: 0098 9133158700. Fax: 0098 3136681679. E-mail: a_fatemi@med.mui.ac.ir Downloaded by [Hacettepe University] at 02:14 11 September 2015