Antibodies to carbonic anhydrase in patients with immune cholangiopathies

doi:10.1016/0016-5085(95)90143-4

Gastroenterology

Volume 108, Issue 6, June 1995, Pages 1802-1809

https://doi.org/10.1016/0016-5085(95)90143-4 Get rights and content

Abstract

$Background/Aims :$ Bile duct epithelia contain an abundance of carbonic anhydrase. Antibodies to this enzyme have been described in autoimmune disorders. Serum from patients with immune-mediated liver diseases was studied to determine whether antibodies to carbonic anhydrase II and/or pyruvate dehydrogenase could distinguish autoimmune cholangitis as immunologically distinct from primary biliary cirrhosis. $Methods :$ Antibody assays to carbonic anhydrase II (Western blot) and pyruvate dehydrogenase (flow cytometry) were performed on the sera of patients with autoimmune cholangitis (6), primary biliary cirrhosis (12), primary sclerosing cholangitis (12), autoimmune hepatitis (12), and control (Gilbert syndrome; 8). $Results :$ Reactivity to carbonic anhydrase II was detected in 5 of 6 patients with autoimmune cholangitis, 1 of 12 patients with primary biliary cirrhosis, 1 of 12 patients with autoimmune hepatitis, and no other patients. Individuals with autoimmune cholangitis were more likely than the other patients to be reactive to carbonic anhydrase II (P < 0.001). Patients with primary biliary cirrhosis were more reactive to pyruvate dehydrogenase compared with all other groups (P < 0.001). $Conclusions :$ An antibody to human carbonic anhydrase II is frequently detected in the sera of patients with autoimmune cholangitis and is uncommon or not present in other cholangiopathies. These data provide evidence that autoimmune cholangitis and primary biliary cirrhosis represent distinct entities with unique patterns of immunoreactivity.

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Antimitochondrial Antibody–Negative Primary Biliary Cholangitis: Is It Really the Same Disease?
2018, Clinics in Liver Disease
Citation Excerpt :
The diagnosis of AMA-negative PBC is challenging due to the heterogeneous histologic findings in each of the 4 stages of PBC and the frequent lack of the classic findings such as the florid duct lesion.11 The literature has been difficult to interpret because many terms are used to define the same disease entity, including AMA-negative PBC, autoimmune cholangitis, primary autoimmune cholangitis, autoimmune cholangiopathy, immunocholangitis, or (even more broadly) the nonspecific term autoimmune liver disease.12–16 Conversely, many diseases with nonspecific autoimmunity may be lumped together, creating a heterogeneous group that may include overlap syndromes (Fig. 1).
Subgroups of Sjögren syndrome patients according to serological profiles
2012, Journal of Autoimmunity
Citation Excerpt :
Up to now a total of 13 active isoenzymes of carbonic anhydrase have been described in mammals [90]. Autoantibodies against the carbonic anhydrase isoenzyme II (anti-CAII) have been detected in the serum of patients with several autoimmune conditions, such as SLE, SS, SSc, dermatomyositis [91], RA [92], PBC [93], autoimmune cholangiitis [94] and Graves thyroiditis [95]. In patients with SS the prevalence of anti-carbonic anhydrase antibodies has been reported in the range of 12.5–20.8% [91,92].
Sjögren Syndrome (SS) is a systemic, autoimmune disorder characterized by lymphocytic infiltration of the exocrine glands. Different clinical associations have been described for each of the diverse autoantibodies found in SS patients. Antibodies directed against the Ro/La ribonucleoprotein complexes have been correlated with younger age, more severe dysfunction of the exocrine glands and a higher prevalence of extraglandular manifestations. Anti-nuclear antibodies and rheumatoid factors have been associated to extraglandular manifestations and an active immunological profile, while cryoglobulins are markers of more severe disease and correlate to lymphoma development and death. Antibodies to cyclic citrullinated peptides are scarce in SS and have been linked in some cases to the development of non-erosive arthritis. Furthermore, the presence of anti-mitochondrial antibodies and anti-smooth muscle antibodies in the sera of primary SS patients is considered indicative of primary biliary cirrhosis and autoimmune hepatitis, respectively. In addition, anti-centromere antibodies have been associated with a clinical phenotype intermediate between primary SS and systemic sclerosis, while antibodies against carbonic anhydrase have been related to renal tubular acidosis. Finally, an association of anti-muscarinic antibodies with cytopenias and a higher disease activity has also been described in primary SS. In conclusion, although not all of the above mentioned antibodies are useful for predicting distinct patient subgroups in SS, knowledge of the clinical associations of the different autoantibody specificities encountered in SS can advance our understanding of the disease and improve patient management.
Autoimmune hepatitis
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Transitions between variant forms of primary biliary cirrhosis during long-term follow-up
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Thus, the prevalence of autoantibodies (ANA and/or SMA) is much higher than seen in AMA-positive PBC [9]. Antibodies directed against a subtype of carbonic anhydrase (CA-II) have been reported to occur more frequently in patients with AIC than in PBC or autoimmune hepatitis (AIH) [10]. Furthermore, IgM concentrations tend to be lower, and IgG concentrations higher in AIC than in PBC [3].
Conditions exhibiting features of two different autoimmune liver diseases are designated overlap syndromes. Variant forms display some, but not all, characteristics of a distinct autoimmune liver disease. We describe transitions over time between variant forms of PBC, i.e. AMA-negative PBC, autoimmune hepatitis (AIH)–PBC overlap and autoimmune cholangitis (AIC) in a large cohort of PBC patients in Sweden.
We retrieved all patients with variant forms of PBC in six university hospitals in Sweden, covering 60% of the Swedish population. The diagnosis of PBC and its variants was based on laboratory findings and compatible histological features. The revised autoimmune hepatitis scoring system proposed by the International Autoimmune Hepatitis Group was used to establish the diagnosis of AIH.
In a population of 800 patients with PBC, we identified 35 (5%) variant forms; 25 patients with AIH–PBC overlap, 8 with AIC and 2 with AMA-negative PBC at the time of our study. The initial diagnoses were PBC (3 patients), AIH (3), AIH–PBC overlap (16), AIC (8) and AMA-negative PBC with (1) or without (4) concomitant AIH. The median follow-up was 125 (41–360) months. Immunosuppression and ursodeoxycholic acid induced a complete or good regression of increased aminotransferases in about half of the patients who were given one or both of these treatments.
Variant forms of PBC are seen in approximately 5% of PBC patients in Sweden. Transition between different forms may occur, emphasizing the value of repeat biopsies, but established overlapping AIH–PBC seems to be stable over time.
Hepatic overlap syndromes
2005, Journal of Hepatology
Citation Excerpt :
Thus, these data indicate that AIC represents an AMA-negative PBC. The specificity of autoantibodies to carbonic anhydrase which had been described in AIC and were proposed as markers of differentiation between AIC and PBC [52] has been questioned [53]. Similarly, antilactoferrin antibodies were identifed in patients with AIC, and lactoferrin was discussed as a potential target antigen in AIC [54].

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^☆: Supported by the William Beaumont Research Institute. Presented at the poster session of the American Gastroenterological Association in New Orleans, Louisiana, May 15–18, 1994, and published in abstract form (Gastroenterology 1994; 106: A900).

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Antibodies to carbonic anhydrase in patients with immune cholangiopathies☆

Abstract

J Dermatol Sci

J Immunol Methods

J Hepatol

Gastroenterology

Gastroenterology

Gastroenterology

Curr Opin Struct Biol

Carbonic anhydrase and the carotid body

Rapid separation of carbonic anhydrase isozymes using cellulose acetate membrane electrophoresis

J Exp Bot

A study of hepatic carbonic anhydrase

Mod Pharmacol

Immunocytochemical demonstration of carbonic anhydrase in human epithelial cells

J Histochem Cytochem

Antibodies to carbonic anhydrase in systemic lupus erythematosus and other rheumatic diseases

Arthritis Rheum

Carbonic anhydrase antibody in sera from patients with endometriosis

Am J Clin Pathol

Antimitochondrial antibody negative primary biliary cirrhosis: a distinct syndrome of autoimmune cholangitis

Gut

A cholangitis with antinuclear antibodies (immuno-cholangitis) resembling chronic non-suppurative destructive cholangitis

Dtsch Med Wochenschr

Autoimmune cholangiopathy: part of the spectrum of autoimmune chronic active hepatitis

Hepatology

Nonsuppurative cholangitis induced in rodents by cholangiocyte immunization: an experimental model for immune cholangiopathies

Hepatology

Natural history, clinical features, and treatment of autoimmune hepatitis

Semin Liver Dis

Meeting report: international autoimmune hepatitis group

Cleavage of structural proteins during assembly of the head of bacteriophage T4

Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets