Antigen specificity of antihistone antibodies in systemic sclerosis

Abstract

Objectives: The aim of the study was to determine the prevalence and clinical significance of antibodies to individual histone components in systemic sclerosis (SSc).

Methods: Serum samples from patients with limited cutaneous SSc (lSSc; n = 42) and diffuse cutaneous SSc (dSSc; n = 28) were examined for IgG and/or IgM antibodies to individual histone components and complexes by enzyme linked immunosorbent assay (ELISA).

Results: The level of IgG antibody to total histones was significantly higher in lSSc and dSSc than in normal controls. The level of IgM antibody to total histones was significantly higher in lSSc, but not in dSSc, than in normal controls. IgG antibody to total histones tended to be increased in dSSc when compared with that in lSSc. On the other hand, IgM antibody to total histones tended to be increased in lSSc when compared with that in dSSc. Although SSc showed various antihistone specificities, H2B, H2A-H2B, (H2A-H2B)-dsDNA were main antigens recognised by IgG antibodies in both lSSc and dSSc. Although IgM antibodies to H2B and H2A-H2B were also detected in both lSSc and dSSc, serum samples from lSSc patients exhibited highest IgM reactivity with H1.

Conclusion: SSc may be included among conditions in which heterogeneous antihistone antibodies are produced. IgM antibodies to the most accessible histone H1 may be related to mild clinical features (lSSc) and IgG antibodies to the inner core molecules of native histone such as H2B or complexes including H2B may be associated with severe clinical features (dSSc) in Ssc.

Figure 1

ELISA for antibody to total histones in serum samples from patients with limited cutaneous systemic sclerosis (lSSc) (n=42), diffuse cutaneous systemic sclerosis (dSSc) (n=28), systemic lupus erythematosus (SLE) (n=22), bullous pemphigoid (BP) (n=20), and normal controls (n=57). Horizontal broken line represents the median value +3 SD of antihistone activity in normal control group. Horizontal short bars represent the median values in each group. (A) Serum IgG reactivity to total histones in lSSc, dSSc, SLE, BP, and normal control. (B) Serum IgM reactivity to total histones in lSSc, dSSc, SLE, BP, and normal control.

Figure 2

Patterns of IgG reactivity of antihistone antibodies with individual histone components and complexes in patients with systemic sclerosis (SSc). Average OD of IgG reactivity to each histone in normal controls was substracted from the OD (mean (SEM)) of IgG reactivity to each histone in patients. (A) IgG reactivity to histones in patients with SSc (n=70), (B) IgG reactivity to histones in patients with limited cutaneous SSc (lSSc) (n=42), (C) IgG reactivity to histones in patients with diffuse cutaneous SSc (dSSc) (n=28).

Figure 3

Patterns of IgM reactivity of antihistone antibodies with individual histone components and complexes in patients with systemic sclerosis (SSc). Average OD of IgM reactivity to each histone in normal controls was substracted from the OD (mean (SEM)) of IgM reactivity to each histone in patients. (A) IgM reactivity to histones in patients with SSc (n=70), (B) IgM reactivity to histones in patients with limited cutaneous SSc (lSSc) (n=42), (C) IgM reactivity to histones in patients with diffuse cutaneous SSc (dSSc) (n=28).