Complement abnormalities in acquired lipodystrophy revisited.
BACKGROUND
Lipodystrophy is a heterogeneous condition characterized by an inherited or acquired deficiency in the number of adipocytes required for the storage of energy as triglycerides. Acquired lipodystrophy is frequently associated with other autoimmune disorders. One well-studied form is characterized by the selective loss of upper body fat in association with activation of the alternative complement pathway by C3 nephritic factor, low complement factor C3, and mesangiocapillary glomerulonephritis.


OBJECTIVE
We now describe an immunologically distinct form of acquired generalized lipodystrophy, with evidence of activation of the classical complement pathway (low C4) and autoimmune hepatitis. Patients and Research Design: Three unrelated patients with acquired lipodystrophy and low complement C4 levels are described. In vitro analysis of the complement pathway was undertaken to determine the reason for the low C4 complement levels. Biopsies were obtained from liver, bone marrow, and adipose tissue for histological analysis.


RESULTS
All three patients manifested near-total lipodystrophy, chronic hepatitis with autoimmune features, and low C4 complement levels. Additional autoimmune diseases, including severe hemolytic anemia, autoimmune thyroid disease, and polyneuropathy, were variably present. Detailed studies of complement pathways suggested constitutive classical pathway activation.


CONCLUSIONS
Although the previously described syndrome, which typically results in a cephalad pattern of partial lipodystrophy, results from activation of the alternative complement pathway, this form, in which lipodystrophy is generalized, is associated with activation of the classical pathway. Future therapeutic approaches to these disorders may benefit from being tailored to their distinct immunopathogenesis.
Savage
David B
DB
Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, United Kingdom. dbs23@medschl.cam.ac.uk
Semple
Robert K
RK
Clatworthy
Menna R
MR
Lyons
Paul A
PA
Morgan
B Paul
BP
Cochran
Elaine K
EK
Gorden
Phillip
P
Raymond-Barker
Philippa
P
Murgatroyd
Peter R
PR
Adams
Claire
C
Scobie
Ian
I
Mufti
Ghulam J
GJ
Alexander
Graeme J M
GJ
Thiru
Sathia
S
Murano
Incoronata
I
Cinti
Saverio
S
Chaudhry
Afzal N
AN
Smith
Kenneth G C
KG
O'Rahilly
Stephen
S
D000328:Adult; D002675:Child, Preschool; D003167:Complement Activation; D003181:Complement C4 / Q000172:deficiency*; D003171:Complement Pathway, Classical; D005260:Female; D006801:Humans; D008060:Lipodystrophy / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008297:Male; D008875:Middle Aged
D003181:Complement C4