Electronic Letters to:

Other Original Articles: Pamela Fischer-Posovszky, Helge Hebestreit, Albert K. Hofmann, Gudrun Strauss, Peter Möller, Klaus-Michael Debatin, and Martin Wabitsch Role of CD95-Mediated Adipocyte Loss in Autoimmune Lipodystrophy J Clin Endocrinol Metab 2006; 91: 1129-1135 [Abstract] [Full text] [PDF]

eLetters: Submit a response to this article

Electronic letters published:

Adipocyte and the complement system

Sujoy Khan, Stephen Holding, Principal Clinical Scientist, Department of Immunology, Hull Royal Infirmary, Hull, HU3 2JZ, UK   (11 January 2006)

Adipocyte and the complement system 11 January 2006
Sujoy Khan, Specialist Registrar Clinical Immunology PathLinks Immunology, Scunthorpe General Hospital, Scunthorpe, DN15 7BH, UK, Stephen Holding, Principal Clinical Scientist, Department of Immunology, Hull Royal Infirmary, Hull, HU3 2JZ, UK Send letter to journal: Re: Adipocyte and the complement system sujoykhan{at}aol.com Sujoy Khan, et al.	The article by Fischer-Posovszky and colleagues (1) (December 20, 2005 issue) reporting the role of CD95-mediated adipocyte apoptosis in a young girl with lipodystrophy was very interesting. However, the authors comment on neither complement levels nor the presence of an autoantibody in the patient. The complement system proteins are now known to play an important role in maintaining the normal physiology of adipose tissue. The alternative pathway C3 convertase (C3bBb) is formed after cleavage of factor B by factor D. Some acquired partial lipodystrophy (APL) patients have increased ‘tickover’ of the alternative pathway due to the presence of C3 nephritic factor (C3Nef), an IgG autoantibody. C3Nef offers ‘protection’ to C3bBb and prevents its dissociation by factor H, which is the regulatory protein. This leads to uncontrolled alternative pathway activation resulting in hypocomplementaemia. Sissons et al. (2) identified hypocomplementaemia and a serum C3 ‘splitting factor’ in lipodystrophy patients and a review by Misra et al. (3) found 83% of APL patients had low complement C3 levels and 22% of patients developed membranoproliferative glomerulonephritis after a median of 8 years following onset of lipodystrophy. The major source of factor D is adipose tissue. Regional differences in factor D expression may be the reason why adipocyte loss is predominant in certain areas in APL patients. Adipocytes have components to generate C3a that behave as acylation stimulating protein, converting fatty acids into triglyceride (4) and also have the intrinsic ability to activate the alternative pathway. C3Nef containing sera have been shown to induce complement-dependent lysis in vitro that is enhanced by IL-1 and TNF-α and induce adipocyte apoptosis (5). Future strategies for specific complement inhibition for therapeutic purposes in APL certainly appear promising. References: 1. Fischer-Posovszky P, Hebestreit H, Hofmann AK, Strauss G, Möller P, Debatin K-M, Wabitsch, M 2005 Role of CD95-mediated adipocyte loss in autoimmune lipodystrophy. J Clin Endocrinol Metab. Dec 20 [Epub ahead of print]. 2. Sissons JG, West RJ, Fallows J, Williams DJ, Boucher BJ, Amos N, Peters DK. 1976. The complement abnormalities of lipodystrophy. N Engl J Med. 294: 461-465. 3. Misra A, Peethambaram A, Garg A. 2004 Clinical features and metabolic and autoimmune derangements in acquired partial lipodystrophy: report of 35 cases and review of the literature. Medicine (Baltimore). 83:18-34. 4. Sniderman AD, Cianflone K. 1994. The adipisin-ASP pathway and regulation of adipocyte function. Ann Med 26:388-393. 5. Mathieson PW, Wurzner R, Oliviera DBG, Lachmann PJ, Peters DK. 1993 Complement-mediated adipocyte lysis by nephritic factor sera. J Exp Med. 177:1827-1831.