Autoantibodies to nonhistone chromosomal proteins HMG‐1 and HMG‐2 in sera of patients with juvenile rheumatoid arthritis

Wittemann, Bettina; Neuer, Gunter; Michels, H.; Truckenbrodt, H; Bautz, Friedlinde A.

doi:10.1002/art.1780330910

Cited by 71 publications

(46 citation statements)

References 17 publications

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“…The pattern of anti-HMG-1/2 antibodies found in children with secondary PHT was also consistent with the autoantibody specificity reported for JRA [24,25]. However, none of these patients fulfilled the diagnostic criteria for SLE [30] or JRA [33], although PHT may present as a forme fruste of these or any CTDs.…”

Section: Discussionsupporting

confidence: 86%

Primary pulmonary hypertension: immunogenetic response to high-mobility group (HMG) proteins and histone

Morse

Barst

Fotino

et al. 1996

Clinical and Experimental Immunology

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SUMMARYHLA class II alleles (DNA typing) and antibodies to HMG-1,2,14,17 proteins and H1 histone were determined in three predominantly Caucasian groups of patients with pulmonary hypertension (PHT). Forty-four adults had primary pulmonary hypertension (PPH), 42 children had PPH, and 41 children had PHT associated with anatomically large congenital pulmonary to systemic shunts (PHT shunt). The HLA class II alleles in the Caucasian patients were compared with those of 51 healthy Caucasian controls. Eight (18%) of 44 sera from adults with PPH bound HMG-14 and 23 (52%) bound H1. None of 42 sera from children with PPH bound either HMG-14/17 or HMG-1/2, whereas four (10%) bound H1. In the PHT shunt group of 41 children, two (5%) bound HMG-14, one (3%) bound HMG-17, four (10%) bound HMG-1 and/or HMG-2, and six (15%) bound H1. Among the 12 HMG antibody-positive patients, HLA-DQ6 was present in nine of 10 HLA typed patients (six PPH adults and three PHT shunt children), seven of whom had antibodies to HMG-14 and one to HMG-17. The 100% frequency of HLA-DQ6 in seven Caucasian patients with antibodies to HMG-14/17 was statistically significant when compared with the 41% frequency of -DQ6 present in 51 healthy Caucasian controls (pc 0 . 027, pc Bonferroni correction, OR 21 . 3). In contrast, when compared with controls, 25 patients with PPH and anti-H1 antibodies (21 adults and four children) had increased frequencies of HLA-DQ7 and -DR5 (60% versus 29%, P 0 . 010, OR 3 . 6 and 48% versus 22%, P 0 . 018, OR 3 . 4), which were not significant after correction. In essence, antibodies to HMG-14 and to H1 proteins were present predominantly in adults with PPH, suggesting that the pattern of response to HMG-14/17 was similar to that previously reported in systemic lupus erythematosus (SLE) and drug-induced autoimmunity. This is the first report of an association between autoantibodies directed against HMG and H1 with immunogenetic markers. These data suggest that a subset of patients with PPH may have an autoimmune disease.

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Section: Discussionsupporting

confidence: 86%

Primary pulmonary hypertension: immunogenetic response to high-mobility group (HMG) proteins and histone

Morse

Barst

Fotino

et al. 1996

Clinical and Experimental Immunology

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“…In our study, anti-HMG1/2 antibodies did not stain the nucleus of ethanolor formalin-fixed neutrophils on IIF. Previous studies also reported that anti-HMG1/2 antibodies stained predominantly the cytoplasm of formaldehyde-fixed HEp-2 cells [23] and methanol-acetonefixed rat liver TR-12 cells [26]. Considering that anti-HMG1/2 antiserum showed a P-ANCA staining pattern of ethanol-fixed neutrophils on IIF, the pathological significance of anti-HMG1/2 antibodies should be studied in terms of not only ANA, but also ANCA.…”

Section: Discussionmentioning

confidence: 94%

“…The presence of antibodies to HMG1 and HMG2 has been reported in sera of patients with systemic lupus erythematosus [22] and juvenile rheumatoid arthritis [23]. It is generally accepted that anti-HMG1/2 antibodies are antinuclear antibodies (ANA) [24].…”

Section: Discussionmentioning

confidence: 99%

Novel autoantigens of perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) in ulcerative colitis: non-histone chromosomal proteins, HMG1 and HMG2

Sobajima

Ozaki

Osakada

et al. 1997

Clinical and Experimental Immunology

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SUMMARYAnti-neutrophil cytoplasmic antibodies (ANCA) in sera from ulcerative colitis (UC) patients have been described as reacting with proteins in the granules of human neutrophils such as cathepsin G and lactoferrin and with yet unidentified antigens. Here we report the existence of a new member of perinuclear ANCA (P-ANCA) in UC patients. In the previous study, we found that UC patients had a novel P-ANCA against neutrophil 28-kD protein. In this study, we purified the same antigens from HL-60 lysates by using reversed phase high-performance liquid chromatography, and revealed that the 28-kD antigen consisted of two different proteins. The N-terminus amino acids of these proteins are identical with those of high mobility group (HMG) non-histone chromosomal proteins HMG1 and HMG2. Immunoblotting analysis of human neutrophil lysates using rabbit anti-HMG1/2 antisera revealed a single band of 28 kD, and the 28-kD band detected by immunoblotting analysis using patient's serum IgG completely disappeared after preincubation with a mixture of HMG1 and HMG2. Furthermore, rabbit anti-HMG1/2 antisera showed a perinuclear staining pattern in indirect immunofluorescence studies using ethanol-fixed neutrophils. These data demonstrate that HMG1 and HMG2 are novel target antigens of P-ANCA. HMG1 and HMG2 are distributed in the nuclei and cytoplasm of eukaryotic cells and act as transcription factors. Their intracellular localization and functions are distinct from those of the previously reported granular antigens of P-ANCA.

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“…In addition, anti-HMGB-1 autoantibodies have been detected in the serum of patients with juvenile rheumatoid arthritis (26). The clinical relevance of TLR activation in RA is supported by enhanced expression of TLRs 2, 3, 4, and 7 in the synovial lining and elevated TLR-2 expression in CD16ϩ peripheral blood monocytes and synovial macrophages from RA patients (25,(27)(28)(29).…”

mentioning

confidence: 99%

Shift from toll‐like receptor 2 (TLR‐2) toward TLR‐4 dependency in the erosive stage of chronic streptococcal cell wall arthritis coincident with TLR‐4–mediated interleukin‐17 production

Abdollahi‐Roodsaz¹,

Joosten²,

Helsen³

et al. 2008

Arthritis & Rheumatism

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Autoantibodies to nonhistone chromosomal proteins HMG‐1 and HMG‐2 in sera of patients with juvenile rheumatoid arthritis

Abstract: Antinuclear antibodies (ANA) have been reported to occur in >50% of patients with juvenile rheumatoid arthritis (JRA) (1-4). Although ANA are

Cited by 71 publications

References 17 publications

Primary pulmonary hypertension: immunogenetic response to high-mobility group (HMG) proteins and histone

Primary pulmonary hypertension: immunogenetic response to high-mobility group (HMG) proteins and histone

Novel autoantigens of perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) in ulcerative colitis: non-histone chromosomal proteins, HMG1 and HMG2

Shift from toll‐like receptor 2 (TLR‐2) toward TLR‐4 dependency in the erosive stage of chronic streptococcal cell wall arthritis coincident with TLR‐4–mediated interleukin‐17 production

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