Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Presence of HMGB1 (High Mobility Group Box 1) and Antibodies to HMGB1 in Systemic Lupus Erythematosus (SLE).

Abdulahad,  Deena, Westra,  Johanna, Limburg,  Pieter, Kallenberg,  Cees, Bijl,  Marc

Background:

Apoptotic cells accumulate in SLE and are considered to play an important role in the pathogenesis. High mobility Group box 1 is a non-histone nuclear protein, that can be secreted actively by inflammatory cells, and is released passively from apoptotic and necrotic cells where it may act as an autoantigen and as a pro-inflammatory mediator. There is increasing evidence that HMGB1 contributes to the pathogenesis of chronic inflammatory and auto-immune diseases. Indeed, presence of HMGB1 in serum of mice with SLE has been reported in the serum of lupus mice.

Objectives:

In this study we determined levels of HMGB1 and anti-HMGB1 in SLE patients compared to healthy controls (HC).Also their relation with clinical and biochemical parameters was assessed.

Methods:

The study population consisted of 69 SLE patients and 35 age and sex matched HC. Of the 69 SLE patients 35 were visiting the outpatient clinic and randomly chosen. The other 34 patients were selected for active disease and paired samples of these patients were selected during inactive phase of the disease. Eighteen of 34 patients had renal involvement and remaining 16 patients had other organ involvement. HMGB1 levels were measured with a Western blot and anti-HMGB1 levels were measured with an in-house developed ELISA using recombinant HMGB1 as antigen. Clinical and biochemical parameters of all patients were assessed routinely.

Results:

HMGB1 levels in all SLE patients were significantly increased compared to HC. HMGB1 levels were relatively more increased in patients with renal involvement compared to non renal patients. HMGB1 levels were correlated with disease activity, as determined by SLEDAI. HMGB1 levels were correlated with anti-dsDNA levels and showed a negative correlation with C3. Anti-HMGB1 levels were significantly increased in all SLE patients compared to HC and were correlated to HMGB1 levels in all SLE patients.

Conclusions:

In SLE patients serum HMGB1 levels are significantly increased, in particular in patients with renal involvement, and are related to disease activity. Furthermore, in SLE patients increased levels of anti-HMGB1 antibodies were detected. Whether HMGB1, and HMGB1-anti-HMGB1 immune complexes play a role in the pathogenesis of SLE, in particular in patients with renal involvement needs to be established.

To cite this abstract, please use the following information:
Abdulahad, Deena, Westra, Johanna, Limburg, Pieter, Kallenberg, Cees, Bijl, Marc; Presence of HMGB1 (High Mobility Group Box 1) and Antibodies to HMGB1 in Systemic Lupus Erythematosus (SLE). [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1195
DOI: 10.1002/art.28961

Abstract Supplement

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