Correlation between expression of antibodies to histone H2B and clinical activity in HIV-infected individuals

Williams, W.; Whalley, Alice; Comacchio, R; Rosenberg, J.; Watts, Richard A.; Isenberg, David; Cutchan, J. A. Mc; Morrow, W. J. W.

doi:10.1046/j.1365-2249.1996.d01-633.x

Cited by 18 publications

(12 citation statements)

References 35 publications

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“…HIV-1 infection is characterized by a plethora of autoimmune phenomena caused by the extreme immune activation. A high prevalence of circulating autoantibodies against a constellation of antigens has been reported in HIV-1-infected patients [5][6][7][8], but their clinical significance is unclear [9]. In a recent report, 2 AIDS patients with anemia caused by pure red cell aplasia (PRCA) responded favorably to prednisone treatment, suggesting the presence of an autoimmune mechanism [10].…”

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confidence: 99%

Circulating Autoantibodies to Erythropoietin Are Associated with Human Immunodeficiency Virus Type 1–Related Anemia

et al. 1999

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In a cohort of 204 unselected consecutive human immunodeficiency virus type 1 (HIV-1)-infected patients, the association of circulating autoantibodies to endogenous erythropoietin (EPO) with HIV-1-related anemia was studied. Circulating autoantibodies to EPO were present in 48 (23.5%) of the 204 patients studied. Circulating autoantibodies were an independent predictor of anemia (odds ratio [OR]=5.0; 95% confidence interval [CI], 2.5-9.9), as strong as other known causes of anemia. The association of anti-EPO antibodies with anemia became stronger when the analysis was limited to the group of patients without any medical condition causing anemia (OR=10.4; 95% CI, 3.2-33.9). Moreover, the effect on hemoglobin levels remained significant even after adjusting for other anemia parameters. Anti-EPO autoantibodies were associated with higher EPO levels (r=.25, P=.012) and with a more prominent EPO response to anemia. Our findings suggest that autoimmunity, among other factors, may contribute to the pathogenesis of HIV-1-related anemia.

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confidence: 99%

Circulating Autoantibodies to Erythropoietin Are Associated with Human Immunodeficiency Virus Type 1–Related Anemia

et al. 1999

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“…Different studies reported a high prevalence of circulating autoantibodies, ranging from 4% for non-organ specific autoantibodies 11 to 47% for histone H2B autoantibodies. 12 However, these studies failed to show clinical significance for any of these autoantibodies. 13 On the contrary, in a previous study 14 we have shown that among HIV-infected patients, circulating anti-EPO autoantibodies were independently associated with lower hemoglobin and higher erythropoietin levels.…”

Section: Discussionmentioning

confidence: 95%

Circulating antibodies to endogenous erythropoietin and risk for HIV-1-related anemia

Tsiakalos

Kordossis

Ziakas

et al. 2010

Journal of Infection

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“…The lack of binding of LG11-2 to this analogue suggests that the terminal residues of the 6 -18 peptide may be involved in direct contact with the LG11-2 binding site or that some of these residues (e.g. Pro 8 , which was replaced in R1 by an acetylated alanine) play a critical role in the overall conformation of the epitope.…”

Section: Resultsmentioning

confidence: 99%

“…Among antibodies to individual core histones, those reacting with histone H2B are a particularly frequent specificity (3)(4)(5)(6). Antibodies to H2B are also encountered in other autoimmune diseases, such as systemic sclerosis (7) as well as in human immunodeficiency virus-infected individuals (8). Anti-H2B antibodies in SLE patients almost always recognize determinants that are located in the amino terminus (residues 1-25) of the histone molecule (9).…”

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confidence: 99%

Molecular and Structural Properties of Three Autoimmune IgG Monoclonal Antibodies to Histone H2B

Monestier¹,

Decker²,

Briand³

et al. 2000

Journal of Biological Chemistry

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In systemic autoimmune diseases such as lupus the immune system produces autoantibodies to nuclear antigens including DNA and histone molecules. In the present study, we describe three monoclonal IgG antibodies that have been obtained from lupus-prone MRL/ lpr mice. These three antibodies react with the amino terminus of histone H2B, a region of the molecule that is accessible in chromatin. Using a series of overlapping H2B synthetic peptides and structural analogues, we have mapped the different epitopes recognized by these antibodies. We have also sequenced the combining sites (variable regions) of the antibodies and modeled their interactions with the corresponding epitopes. Overall, the data suggest that the mechanisms of interaction with antigen are different for each of the three antibodies, even though they all react with the amino-terminal domain of the histone H2B molecule. The results also suggest that the binding between these antibodies and histone H2B is different from that between most antibodies and conventional protein antigens since the heavy chain complementarity-determining region 3 appears to play only a limited role in the three antibodies tested. The study of the interaction between self-antigens and spontaneously occurring autoantibodies may help us elucidate the mechanisms driving the expansion of self-reactive lymphocytes.In systemic autoimmune diseases such as systemic lupus erythematosus (SLE), 1 self-reactive B cells produce autoantibodies against nucleosomes, the building blocks of chromatin. The nucleosome core particle is composed of a central octamer of two molecules of each of the histones H2A, H2B, H3, and H4, surrounded by approximately two turns of DNA (1). The core histones interact among themselves via their central globular domains, whereas the positively charged amino termini of these histones are accessible on the external surface of the nucleosome core particle (1). Histone H1 binds outside the core particle to the linker DNA (20 -60 base pairs), joining adjacent core particles to form the nucleosomal array.SLE autoantibodies can recognize a diverse array of epitopes located on the surface of the nucleosome. Some SLE antinuclear antibodies can recognize multimolecular determinants, whereas other antibodies are directed against individual components such as DNA or histones, reviewed in (2). Among antibodies to individual core histones, those reacting with histone H2B are a particularly frequent specificity (3-6). Antibodies to H2B are also encountered in other autoimmune diseases, such as systemic sclerosis (7) as well as in human immunodeficiency virus-infected individuals (8). Anti-H2B antibodies in SLE patients almost always recognize determinants that are located in the amino terminus (residues 1-25) of the histone molecule (9). Several mouse strains, such as the autoimmune MRL/lpr mice, spontaneously develop a syndrome with autoantibody production and glomerulonephritis that resembles SLE (10). In the present study, we report the molecular and structural characterist...

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Correlation between expression of antibodies to histone H2B and clinical activity in HIV-infected individuals

Cited by 18 publications

References 35 publications

Circulating Autoantibodies to Erythropoietin Are Associated with Human Immunodeficiency Virus Type 1–Related Anemia

Circulating Autoantibodies to Erythropoietin Are Associated with Human Immunodeficiency Virus Type 1–Related Anemia

Circulating antibodies to endogenous erythropoietin and risk for HIV-1-related anemia

Molecular and Structural Properties of Three Autoimmune IgG Monoclonal Antibodies to Histone H2B

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