Liver autoantibodies in patients with scleroderma

Skare, Thelma Larocca; Nisihara, Renato; Haider, Osvaldo; Azevedo, Pedro Ming; Utiyama, Shirley Ramos da Rosa

doi:10.1007/s10067-010-1586-0

Cited by 15 publications

(10 citation statements)

References 19 publications

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“…PBC is serologically characterized by a high titre of AMA, of which the major targets are PDC-E2, OGDC-E2 and BCOADC-E2 (24). However, AMA has also been detected in sera from patients with other diseases, including SjS (25), scleroderma (26) and ALF (27). Consistent with these reports, we also observed seropositivity of AMA in scleroderma, ALF and PSC (Table 1) in our study.…”

Section: Discussionsupporting

confidence: 91%

Anti‐kelch‐like 12 and anti‐hexokinase 1: novel autoantibodies in primary biliary cirrhosis

Norman

Yang

Ostendorff

et al. 2014

Liver International

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Background Using high-density human recombinant protein microarrays, we identified two potential biomarkers, kelch-like 12 (KLHL12) and hexokinase-1 (HK1), in primary biliary cirrhosis (PBC). The objective of this study was to determine the diagnostic value of anti-KLHL12/HK1 autoantibodies in PBC. Aims Initial discovery used sera from 22 patients with PBC and 62 non-PBC controls. KLHL12 and HK1 proteins were then analyzed for immunoglobulin reactivity by immunoblot and enzyme-linked immunosorbent assay (ELISA) in two independent cohorts of PBC and disease/healthy control patients. Methods Serum samples from 100 patients with PBC and 165 non-PBC disease controls were analyzed by immunoblot and samples from 366 patients with PBC, 174 disease controls, and 80 healthy donors were tested by ELISA. Results Anti-KLHL12 and anti-HK1 antibodies were each detected more frequently in PBC compared with non-PBC disease controls (p < 0.001). Not only are both markers highly specific for PBC (≥ 95%), but they also yielded higher sensitivity than anti-gp210 and anti-sp100 antibodies. Combining anti-HK1 and anti-KLHL12 with available markers (MIT3, gp210 and sp100) increased the diagnostic sensitivity for PBC. Most importantly, anti-KLHL12 and anti-HK1 antibodies were present in 10~35% of AMA-negative PBC patients and adding these two biomarkers to conventional PBC assays dramatically improved the serological sensitivity in AMA-negative PBC from 55% to 75% in immunoblot and 48.3% to 68.5% in ELISA. Conclusions The addition of tests for highly specific anti-KLHL12 and anti-HK1 antibodies to AMA and ANA serological assays significantly improves efficacy in the clinical detection and diagnosis of PBC, especially for AMA-negative subjects.

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Section: Discussionsupporting

confidence: 91%

Anti‐kelch‐like 12 and anti‐hexokinase 1: novel autoantibodies in primary biliary cirrhosis

Norman

Yang

Ostendorff

et al. 2014

Liver International

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“…Table 2 summarises the clinical relevance of the nine cytoplasmic HEp-2 IIFA patterns, that is, AC-15–AC-23 26 33 80–101. It is recognised that the distinction between AC-19 (dense fine speckled) and AC-20 (fine speckled) can be challenging.…”

Section: Resultsmentioning

confidence: 99%

Clinical relevance of HEp-2 indirect immunofluorescent patterns: the International Consensus on ANA patterns (ICAP) perspective

Damoiseaux

Andrade

Carballo³

et al. 2019

Ann Rheum Dis

229

281

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The indirect immunofluorescence assay (IIFA) on HEp-2 cells is widely used for detection of antinuclear antibodies (ANA). The dichotomous outcome, negative or positive, is integrated in diagnostic and classification criteria for several systemic autoimmune diseases. However, the HEp-2 IIFA test has much more to offer: besides the titre or fluorescence intensity, it also provides fluorescence pattern(s). The latter include the nucleus and the cytoplasm of interphase cells as well as patterns associated with mitotic cells. The International Consensus on ANA Patterns (ICAP) initiative has previously reached consensus on the nomenclature and definitions of HEp-2 IIFA patterns. In the current paper, the ICAP consensus is presented on the clinical relevance of the 29 distinct HEp-2 IIFA patterns. This clinical relevance is primarily defined within the context of the suspected disease and includes recommendations for follow-up testing. The discussion includes how this information may benefit the clinicians in daily practice and how the knowledge can be used to further improve diagnostic and classification criteria.

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“…Autoimmune hepatitis, idiopathic portal hypertension, and primary sclerosing cholangitis are the other liver diseases that have been reported in patients with SSc. Owing to the autoimmune nature of SSc, some patients may harbor anti‐liver kidney microsomal antibodies (anti‐LKM) or anti‐smooth muscle antibodies (anti‐SMA) in the absence of liver disease …”

Section: Resultsmentioning

confidence: 99%

Review article: pathogenesis and clinical manifestations of gastrointestinal involvement in systemic sclerosis

Kumar

Singh

Rattan

et al. 2017

Aliment Pharmacol Ther

106

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SUMMARY Background Gastrointestinal tract involvement is a common cause of debilitating symptoms in patients with systemic sclerosis. There are no disease modifying therapies for this condition and the treatment remains symptomatic, largely owing to the lack of a clear understanding of its pathogenesis. Aim To investigate novel aspects of the pathogenesis of gastrointestinal involvement in systemic sclerosis To summarize existing knowledge regarding the cardinal clinical gastrointestinal manifestations of systemic sclerosis and its pathogenesis, emphasizing recent investigations that may be valuable in identifying potentially novel therapeutic targets. Methods Electronic (Pubmed/Medline) and manual Google search Results The gastrointestinal tract is the most common internal organ involved in systemic sclerosis. Any part of the gastrointestinal tract from the mouth to the anus can be affected. There is substantial variability in clinical manifestations and disease course and symptoms are non-specific and overlapping for a particular anatomical site. Gastrointestinal involvement can occur in the in the absence of cutaneous disease. Up to 8% of systemic sclerosis patients develop severe gastrointestinal tract symptoms. This subset of patients display increased mortality with only 15% survival at 9 years. Dysmotiity of the gastrointestinal tract causes the majority of symptoms. Recent investigations have identified a novel mechanism in the pathogenesis of gastrointestinal tract dysmotility mediated by functional anti-muscarinic receptor autoantibodies. Conclusion Despite extensive investigation the pathogenesis of gastrointestinal involvement in systemic sclerosis remains elusive. Although treatment currently remains symptomatic, an improved understanding of novel pathogenic mechanisms may allow the development of potentially highly effective approaches including intravenous immunoglobulin and microRNA based therapeutic interventions.

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Liver autoantibodies in patients with scleroderma

Cited by 15 publications

References 19 publications

Anti‐kelch‐like 12 and anti‐hexokinase 1: novel autoantibodies in primary biliary cirrhosis

Anti‐kelch‐like 12 and anti‐hexokinase 1: novel autoantibodies in primary biliary cirrhosis

Clinical relevance of HEp-2 indirect immunofluorescent patterns: the International Consensus on ANA patterns (ICAP) perspective

Review article: pathogenesis and clinical manifestations of gastrointestinal involvement in systemic sclerosis

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