Anti-carbonic Anhydrase II Antibodies in Systemic Sclerosis: Association with Lung Involvement

Alessandri, Cristiano; Bombardieri, Michèle; Viganego, Federico; Conti, Fabrizio; Luca, N; Riccieri, Valeria; Valesini, Guido

doi:10.1080/0891693031000079239

Cited by 12 publications

(8 citation statements)

References 24 publications

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“…Bicarbonate ions facilitate fluid secretions of the salivary glands and, at the same time, serve as a primary mucosal defence by neutralizing the acidic condition in the oesophagus and stomach. Antibody to Car2 has been implicated in a number of autoimmune diseases such as autoimmune chronic pancreatitis [33], T1D [52], systemic sclerosis [53], autoimmune cholangitis [54], primary biliary cirrhosis and SjS [55]. The presence of anti‐carbonic anhydrase autoantibodies in SjS patients focuses attention on an important issue.…”

Section: Discussionmentioning

confidence: 99%

Sjögren's Syndrome‐Like Disease of C57BL/6.NOD‐Aec1 Aec2 Mice: Gender Differences in Keratoconjunctivitis Sicca Defined by a Cross‐Over in the Chromosome 3 Aec1 Locus

Nguyen

Singson²,

Kim³

et al. 2006

Scand J Immunol

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Sjögren's syndrome (SjS) is a systemic autoimmune disease in which an immunological attack primarily against the salivary and lacrimal glands results in loss of acinar cell tissue and function leading to stomatitis sicca and keratoconjunctivitis sicca. In recent years, the NOD mouse has become an accepted model of SjS, exhibiting a spontaneously developing disease that strongly mimics the human condition. Two genetic regions, one on chromosome 1 (designated Aec2) and the second on chromosome 3 (designated Aec1) of NOD mice, have been shown to be necessary and sufficient to recapitulate SjS‐like disease in non‐susceptible C57BL/6 mice. Here we describe a newly derived strain, C57BL/6.NOD‐Aec1R1Aec2, in which a recombination in Aec1 has resulted in reducing this genetic region to less than 20 cM from 48.5 cM. Profiling of this recombinant inbred strain has revealed that male mice maintain a full SjS‐like disease, whereas female mice exhibit stomatitis sicca in the absence of detectable keratoconjunctivitis sicca. These data suggest SjS‐like disease in the NOD mouse shows gender‐specific regulation determined by autosomal genes.

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Section: Discussionmentioning

confidence: 99%

Sjögren's Syndrome‐Like Disease of C57BL/6.NOD‐Aec1 Aec2 Mice: Gender Differences in Keratoconjunctivitis Sicca Defined by a Cross‐Over in the Chromosome 3 Aec1 Locus

Nguyen

Singson²,

Kim³

et al. 2006

Scand J Immunol

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“…Accordingly, caution should be used in interpreting previous data on the prevalence and clinical relevance of these autoantibodies. As to the putative pathogenic role of ACA, significantly higher levels of ACAII in patients affected with Systemic Sclerosis (SSc) with restrictive lung disease (RLD) were found in comparison to SSc patients without lung involvement and healthy controls (6). Since CAlI isoform is abundantly present in alveolar epithelial cells and bronchial glands (13)(14)(15)(16), a possible pathogenic role of ACAII in the development of lung damage in SSc was suggested.…”

mentioning

confidence: 99%

Antibodies to Carbonic Anhydrase in Patients with Connective Tissue Diseases: Relationship with Lung Involvement

Caccavo

Afeltra

Rigon

et al. 2008

Int J Immunopathol Pharmacol

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The aim of this study is to evaluate the presence of antibodies to carbonic anhydrase I and/or II (ACAI and ACAII) in patients affected by connective tissue diseases (CTD) and to investigate their association with lung involvement evaluated by High resolution CT scan (HRCT). Ninety-six patients affected by CTD were studied, i.e, 33 rheumatoid arthritis (RA), 8 psoriatic arthritis (PA), 8 ankylosing spondilitis (AS), 23 Systemic Lupus Erythematosus (SLE), 10 Sjogren Syndrome (SS), and 14 Systemic Sclerosis (SSc). ACA were detected by ELISA. The lung involvement was evaluated by means of a previously described HRCT score. According to a receiver operator characteristic curve, patients were divided into those with HRCT score z 10 and those with HRCT score < 10, where HRCT score ;::: 10 was predictive of interstitial lung disease. ACAI and/or ACAII were detected in 30/96 patients (31.2%) (P

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“…Anti-CAII autoantibodies are also found in autoimmune diseases such as systemic lupus erythematosus, Sjögren’s syndrome, autoimmune cholangitis, chronic pancreatitis, primary biliary cirrhosis, endometriosis, systemic sclerosis, and type I diabetes {Taniguchi, 2003 #1371;Bataller, 2004#1348;Frulloni, 2000#1359;Itoh, 1992#1360;Alessandri, 2003#1372;D’Cruz, 1996 #1374;Invernizzi, 1998#380}. In all of these conditions, antibody levels of anti-CA II were higher in patients with disease than in the control group as reported from 3.8 – 10% in normal subjects.…”

Section: Discussionmentioning

confidence: 99%

Autoimmunity against carbonic anhydrase II affects retinal cell functions in autoimmune retinopathy

Adamus

Karren

2009

Journal of Autoimmunity

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Autoantibodies against various retinal proteins, including anti-carbonic anhydrase II (CAII) autoantibodies, have been found in patients with cancer-associated retinopathy and autoimmune retinopathy without diagnosed cancer. We studied sera from retinopathy patients that showed reactivity with a 30-kDa retinal protein, which was identified as carbonic anhydrase II (CAII), and immunolabeled cells in human retina. The goal of the study was to examine whether patients’ autoantibodies induce pathogenic effects on the catalytic function of CAII, which may have metabolic consequences on cell survival. Our findings revealed that anti-CAII autoantibodies have the capacity to induce cellular damage by impairing CAII cellular function through inhibiting the catalytic activity of CAII in a dose dependent manner, decreasing intracellular pH, increasing intracellular calcium, which in effect decreases retinal cell viability. The destabilized catalytic function of CAII and alterations in cytosolic pH were found very early, suggesting that autoantibodies are the inducers of apoptosis. In summary, our study showed that anti-CAII autoantibodies provoke pathogenic effects on retinal cells by decreasing cell survival by blocking the CAII cellular functions. The current experiments may facilitate better understanding the role of the immune system in retinal degeneration and help to develop better strategies for therapy of autoimmune retinopathy.

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Anti-carbonic Anhydrase II Antibodies in Systemic Sclerosis: Association with Lung Involvement

Cited by 12 publications

References 24 publications

Sjögren's Syndrome‐Like Disease of C57BL/6.NOD‐Aec1 Aec2 Mice: Gender Differences in Keratoconjunctivitis Sicca Defined by a Cross‐Over in the Chromosome 3 Aec1 Locus

Sjögren's Syndrome‐Like Disease of C57BL/6.NOD‐Aec1 Aec2 Mice: Gender Differences in Keratoconjunctivitis Sicca Defined by a Cross‐Over in the Chromosome 3 Aec1 Locus

Antibodies to Carbonic Anhydrase in Patients with Connective Tissue Diseases: Relationship with Lung Involvement

Autoimmunity against carbonic anhydrase II affects retinal cell functions in autoimmune retinopathy

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