demonstrate that anti-C1q autoantibodies can result in a similarly amplified biologic effect of match in vivo locally in the kidney, presumably by generating additional C3 through the classical pathway. would (16). Trouw et al. demonstrate that anti-C1q autoantibodies can result in a AdipoRon similarly amplified biologic effect of match in vivo locally AdipoRon in the kidney, presumably by generating additional C3 through the classical pathway. With this light, it would be of some interest to determine the precise mechanism by which the classical pathway is definitely amplified by JL-1 and whether this antibody interferes with additional classical pathway regulatory mechanisms. Additional deleterious tasks potentially played by anti-C1q autoantibodies In the larger context of lupus-like autoimmunity, C1q offers taken on an increasingly important role and is necessary not only for classical pathwayCdependent match activation in target organs, as focused upon by Trouw et al. in this problem (6), but is also required to directly recognize and help to clear potentially dangerous nuclear autoantigens from apoptotic cells (17). Therefore, in individuals (18) and in certain autoimmune mouse strains (19), the absence of C1q prospects to the development of anti-DNA antibodies and SLE. Of interest, C1q-deficient patients generally exhibit severe renal disease (18), the cause of which has been ascribed to nonCcomplement-dependent mechanisms, as C3 is not required in mice to develop glomerular injury in the absence of C1q (20). With this context of multiple tasks for C1q, one could hypothesize that anti-C1q autoantibodies not only affect individuals with SLE by injuring the kidney, as suggested by Trouw et al. (6), but also by enhancing the development of anti-DNA and additional glomerular-targeting nuclear autoantibodies, because there is too little C1q available for effective clearance of these dangerous antigens (Number ?(Number1C).1C). Therefore, these autoantibodies would not only amplify local injury but also potentially accelerate the development of antinuclear autoantibodies by interfering with C1q clearance functions (21). On the other hand, if these autoantibodies also lead to enhanced match AdipoRon activation at sites where C1q is definitely realizing nuclear antigens, this could in principle switch noninflammatory acknowledgement of apoptotic body by C1q and its receptors to inflammatory acknowledgement when C5a and additional match activation fragments will also be generated, and their receptors are engaged on cells clearing these antigens. In sum, acquired anti-C1q autoantibodies could use several possible mechanisms by which they could increase the severity of an autoimmune response and glomerulonephritis. The studies by Trouw et al. (6) provide an important conceptual advance in this area and open up the possibility of determining how inhibiting C1q or modulating its effects leads to severe SLE. In particular, the use of Epha2 JL-1 and related monoclonal antibodies in mouse models should allow these and additional investigators to better understand the molecular mechanisms that lead both to improved development of anti-DNA antibodies and to cells injury. Footnotes See the related article beginning on page 679. Nonstandard abbreviations used: Mac pc, membrane attack complex; SLE, systemic lupus erythematosus. Discord of interest: The author has declared that no discord of interest is present..