Acquired Generalized Lipodystrophy Associated with Autoimmune Hepatitis and Low Serum C4 Level

Eren, Erdal; Özkan, Tanju; Çakır, Esra Deniz Papatya; Sağlam, Halil; Tarım, Ömer

doi:10.4274/jcrpe.v2i1.39

Cited by 15 publications

(5 citation statements)

References 26 publications

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“…On the other hand, as expected, leptin levels were drastically diminished in these individuals. Low leptin levels have been associated with the activation of the classical complement pathway and low levels of complement C4 in some cases of AGL throughout the literature [26,27] and in one patient in this case series. This inappropriate complement activation may also contribute to the development of autoimmune disorders.…”

Section: Discussionsupporting

confidence: 52%

Clinical Characterisation and Comorbidities of Acquired Generalised Lipodystrophy: A 14-Year Follow-Up Study

Fernandez-Pombo,

Prado-Moraña,

Diaz-Lopez

et al. 2023

JCM

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Acquired generalised lipodystrophy (AGL) is a rare disorder characterised by the gradual loss of fat that tends to generalise over time, the origin of which is still not fully clarified. The aim of this study was to offer a detailed description of seven patients with AGL (five women, 33.8 ± 18.6 years of age), evaluated over the last 14 years, in order to augment the knowledge of this disorder. The onset of the phenotype occurred during childhood and adolescence in five cases, and in adulthood in two cases. Three patients reported infections or vaccine administration prior to the development of lipodystrophy, and two subjects reported nodular swelling. The most frequent physical features were phlebomegaly, umbilical protrusion/hernia, and acanthosis nigricans. Skinfolds and body composition analysis showed the generalised absence of fat, with the exception of one patient in whom fat loss was spared in the trunk. The loss of fat in the palms/soles was observed in five subjects. Regarding metabolic comorbidities, throughout follow-up, two patients developed type 1 diabetes and one type 2 diabetes; three also presented hypertriglyceridaemia, one of whom developed acute pancreatitis, and no macrovascular complications were observed. Only one patient showed decreased complement C4. Autoimmunity was present in all cases, and six patients manifested Hashimoto’s thyroiditis, type 1 diabetes, autoimmune hepatitis, and/or celiac disease. Thus, there are certain clinical characteristics of AGL that may be considered important diagnostic criteria to differentiate this disorder from other lipodystrophy subtypes.

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Section: Discussionsupporting

confidence: 52%

Clinical Characterisation and Comorbidities of Acquired Generalised Lipodystrophy: A 14-Year Follow-Up Study

Fernandez-Pombo,

Prado-Moraña,

Diaz-Lopez

et al. 2023

JCM

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“…One possible explanation is that P is not the target of proteolytic cleavages and its consumption during the activation of the AP is unlikely. Activation of the classic pathway (CP), resulting in low C4, has been described in some patients with acquired generalized lipodystrophy (AGL), though not being considered an specific feature of this pathology [26,27]. In our study, C4 levels were significantly lower in BSS patients compared to controls (Fig.…”

Section: Discussionmentioning

confidence: 45%

Immunological features of patients affected by Barraquer-Simons syndrome

Corvillo

Ceccarini

Nozal

et al. 2020

Orphanet J Rare Dis

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Background: C3 hypocomplementemia and the presence of C3 nephritic factor (C3NeF), an autoantibody causing complement system over-activation, are common features among most patients affected by Barraquer-Simons syndrome (BSS), an acquired form of partial lipodystrophy. Moreover, BSS is frequently associated with autoimmune diseases. However, the relationship between complement system dysregulation and BSS remains to be fully elucidated. The aim of this study was to provide a comprehensive immunological analysis of the complement system status, autoantibody signatures and HLA profile in BSS. Thirteen subjects with BSS were recruited for the study. The circulating levels of complement components, C3, C4, Factor B (FB) and Properdin (P), as well as an extended autoantibody profile including autoantibodies targeting complement components and regulators were assessed in serum. Additionally, HLA genotyping was carried out using DNA extracted from peripheral blood mononuclear cells. Results: C3, C4 and FB levels were significantly reduced in patients with BSS as compared with healthy subjects. C3NeF was the most frequently found autoantibody (69.2% of cases), followed by anti-C3 (38.5%), and anti-P and anti-FB (30.8% each). Clinical data showed high prevalence of autoimmune diseases (38.5%), the majority of patients (61.5%) being positive for at least one of the autoantibodies tested. The HLA allele DRB1*11 was present in 54% of BSS patients, and the majority of them (31%) were positive for *11:03 (vs 1.3% allelic frequency in the general population). Conclusions: Our results confirmed the association between BSS, autoimmunity and C3 hypocomplementemia. Moreover, the finding of autoantibodies targeting complement system proteins points to complement dysregulation as a central pathological event in the development of BSS.

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“…However, the target autoantigen/s have not been yet identified. In addition, some patients have been reported to have chronic hepatitis with autoimmune features and low complement C4 levels, suggesting involvement of the complement classical pathway in the pathogenesis of fat loss ( 5 , 6 ). Unlike in AGL, scientific evidences exist for the involvement of complement-dependent cytotoxicity in the lysis of adipocytes in patients with acquired partial lipodystrophy (APL) ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

Autoantibodies Against Perilipin 1 as a Cause of Acquired Generalized Lipodystrophy

et al. 2018

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Acquired generalized lipodystrophy (AGL) is a rare condition characterized by an altered distribution of adipose tissue and predisposition to develop hepatic steatosis and fibrosis, diabetes, and hypertriglyceridemia. Diagnosis of AGL is based on the observation of generalized fat loss, autoimmunity and lack of family history of lipodystrophy. The pathogenic mechanism of fat destruction remains unknown but evidences suggest an autoimmune origin. Anti-adipocyte antibodies have been previously reported in patients with AGL, although their involvement in the pathogenesis has been poorly studied and the autoantibody target/s remain/s to be identified. Using a combination of immunochemical and cellular studies, we investigated the presence of anti-adipocyte autoantibodies in patients with AGL, acquired partial lipodystrophy, localized lipoatrophy due to intradermic insulin injections or systemic lupus erythematosus. Moreover, the impact of anti-adipocyte autoantibodies from AGL patients was assessed in cultured mouse preadipocytes. Following this approach, we identified anti-perilipin 1 IgG autoantibodies in the serum of patients with autoimmune variety-AGL, but in no other lipodystrophies tested. These autoantibodies altered the ability of perilipin 1 to regulate lipolysis in cultured preadipocytes causing abnormal, significantly elevated basal lipolysis. Our data provide strong support for the conclusion that perilipin 1 autoantibodies are a cause of generalized lipodystrophy in these patients.

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Acquired Generalized Lipodystrophy Associated with Autoimmune Hepatitis and Low Serum C4 Level

Cited by 15 publications

References 26 publications

Clinical Characterisation and Comorbidities of Acquired Generalised Lipodystrophy: A 14-Year Follow-Up Study

Clinical Characterisation and Comorbidities of Acquired Generalised Lipodystrophy: A 14-Year Follow-Up Study

Immunological features of patients affected by Barraquer-Simons syndrome

Autoantibodies Against Perilipin 1 as a Cause of Acquired Generalized Lipodystrophy

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