Journal of Autoimmunity (1997) 10, 415–423 Correlation between Anti-C1q and Immune Conglutinin Levels, but not between Levels of Antibodies to the Structurally Related Autoantigens C1q and Type II Collagen in SLE or RA Johan Ro ¨ nnelid 1 , Iva Gunnarsson 1 , Kristina Nilsson-Ekdahl 2 and Bo Nilsson 2 1 Department of Medicine, Rheumatology Unit, Karolinska Hospital, Stockholm, Sweden 2 Department of Clinical Immunology and Transfusion Medicine, University Hospital, Uppsala, Sweden Received 7 March 1997 Accepted 3 April 1997 The simultaneous appearance of autoantibodies with either a functional or structural relationship to anti-C1q antibodies (anti-C1q) was investigated in 39 systemic lupus erythematosus (SLE) patients and in 28 rheumatoid arthritis (RA) patients, in both cross-sectional and longitudinal design. Levels of anti-C1q showed an isotype-specific correlation to levels of immune con- glutinin (IK) in SLE patients, whereas no correlation was evident to levels of antibodies to the structurally related antigen type II collagen (anti-CII) in SLE or RA patients. IgG anti-C1q levels correlated with serum levels of the terminal complement complex (sC5b-9) in SLE patients. In two longi- tudinally followed patients, the IK response preceded the anti-C1q response. Possibilities for regulation of the humoral anti-complement response are discussed. © 1997 Academic Press Limited Key words: anti-C1q, immune complex, immune conglutinin, rheumatoid arthritis, SLE Introduction Autoantibodies reacting with the collagen-like region (CLR) of the C1q molecule (anti-C1q), have been reported in immune-complex associated diseases, par- ticularly in systemic lupus erythematosus (SLE) [1–3], but also in rheumatoid arthritis (RA) [4] and other diseases [5]. In SLE patients, anti-C1q increases before renal exacerbations [6], and after initiation or increase in steroid therapy a marked decrease both in produc- tion and occurrence of anti-C1q in blood of SLE patients has been described [7]. Immune conglutinins (IK) are autoantibodies reacting with fragments of complement components C3 and C4, present in inflammatory states and in autoimmune diseases. IK are usually of IgM class, but increased levels of IgG IK have been demonstrated in SLE [8, 9]. As with anti- C1q, they react only with surface-bound molecules and not with the complement fragments in fluid phase. In serial investigations performed in SLE patients, IK have been demonstrated to increase sig- nificantly at the time of exacerbation of disease [9]. Autoantibodies to type II collagen (anti-CII) have been described in a subset of patients with RA [10, 11], and have been described as rather common in SLE, being more prevalent in patients with deforming arthritis [12, 13]. Immunological interest has emerged from the structural similarity between CII and C1q. For poly- clonal anti-CII antibodies, a cross-reactivity with enzymatically altered C1q has been described [14], and for a monoclonal anti-CII antibody, an epitope common to CII and C1q has been mapped to the CLR, the same antibody being shown to inhibit C1q activity dose-dependently [15, 16]. An epitope common to CII and C1q has demonstrated arthritis-modulating characteristics [17, 18]. The results obtained with monoclonal antibodies concerning cross-reactivity between CII and C1q have not been reproducible for polyclonal antibodies obtained from RA and SLE patients. In one study, neither competitive inhibition of ELISA measurements nor pre-adsorbtion studies with both antigens demon- strated any cross-reactivity between anti-CII and anti- C1q in RA or SLE sera [19], and in a recent study of IgG anti-C1q antibodies in SLE, adsorption and elution with anti C1q CLR did not suggest any cross- reactivity between the two antigens [20]. However, in a recent study by Trinder et al . [21], fractionated RA synovial fluids (SF) bound to CII and to C1q in the 7S IgG fraction. Although all SF samples binding CII also bound C1q, the converse was not true, as 9/25 C1q binding SF samples did not bind to CII. Simultaneous antibody binding was also noted to peptides from the CLR of C1q and from the cyanogen bromide fragment 11 of CII, both of which express the common amino acid sequence KGEQG [21]. Any covariation with anti-C1q production could thus be dependent on either structural similarity, as in the case of anti-CII, or on a common functional Correspondence to: Johan Ro ¨ nnelid, Research Department of Rheumatology, Centre for Molecular Medicine, L8:07, Karolinska Hospital, S-17176 Stockholm, Sweden. E-mail: Johan.Ronnelid@cmm.ki.se. 415 0896-8411/97/040415+09 $25.00/0/au970147 © 1997 Academic Press Limited