Antibodies to Hmg Proteins in Patients with Drug‐Induced Autoimmunity

Ayer, Linda M.; Rubin, Robert L.; Dixon, Gordon H.; Fritzler, Marvin J.

doi:10.1002/art.1780370115

Cited by 38 publications

(26 citation statements)

References 13 publications

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“…Anti-HMGB1 antibodies are present in the serum of patients with rheumatoid arthritis and drug-induced systemic lupus erythematosus (85,86). Furthermore, HMGB1 has been found to be overexpressed in the extracellular milieu of synovial biopsy specimens in rheumatoid and experimental arthritis (87,88).…”

Section: Hmgb1 and Autoimmunitymentioning

confidence: 99%

HMGB1: Endogenous Danger Signaling

Klune

Dhupar

Cardinal

et al. 2008

Mol Med

683

519

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While foreign pathogens and their products have long been known to activate the innate immune system, the recent recognition of a group of endogenous molecules that serve a similar function has provided a framework for understanding the overlap between the inflammatory responses activated by pathogens and injury. These endogenous molecules, termed alarmins, are normal cell constituents that can be released into the extracellular milieu during states of cellular stress or damage and subsequently activate the immune system. One nuclear protein, High mobility group box-1 (HMGB1), has received particular attention as fulfilling the functions of an alarmin by being involved in both infectious and non-infectious inflammatory conditions. Once released, HMGB1 signals through various receptors to activate immune cells involved in the immune process. Although initial studies demonstrated HMGB1 as a late mediator of sepsis, recent findings indicate HMGB1 to have an important role in models of non-infectious inflammation, such as autoimmunity, cancer, trauma, and ischemia reperfusion injury. Furthermore, in contrast to its pro-inflammatory functions, there is evidence that HMGB1 also has restorative effects leading to tissue repair and regeneration. The complex functions of HMGB1 as an archetypical alarmin are outlined here to review our current understanding of a molecule that holds the potential for treatment in many important human conditions.

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Section: Hmgb1 and Autoimmunitymentioning

confidence: 99%

HMGB1: Endogenous Danger Signaling

Klune

Dhupar

Cardinal

et al. 2008

Mol Med

683

519

View full text Add to dashboard Cite

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“…Of interest, antibodies to HMG-1/2 were not found in adults with PPH. Normal sera have previously been shown not to have antibodies to HMG proteins or to H1 [22,23].…”

Section: Discussionmentioning

confidence: 99%

“…HMG fractions were purified by cation exchange high pressure liquid chromatography (HPLC). The HMG proteins in the HPLC fractions were identified by their elution positions and mobilities in acid-urea polyacrylamide gels [22]. To characterize the HMG fractions in SDS-polyacrylamide (15%) gels, the HPLC-purified fractions were used for initial immunoblotting experiments.…”

Section: Methodsmentioning

confidence: 99%

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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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“…The latter patients are usually carriers of HLA DR 0301, which is a recognized predisposing factor for DIL (Bonaci-Nikolic B et al, 2005, Morrow JD et al, 1953, Yung & Richardson 1994. There are different ANA that are responsible for DIL (Yung &Richardson, 1994;Burlingame & Rubin, 1996;Ayer LM, 1994). These can be directed against MPO, human leukocyte elastase (HLE), catepsin G, lactoferrin and azurocidine, but they all have in common that they affect the neutrophils and monocytes in the perinuclear area (Jennette JC, 2000).…”

Section: Epidemiology Of Small Vessel Vasculitismentioning

confidence: 99%