Low-Avidity Antibodies to Carbonic Anhydrase-I and -II in Autoimmune Chronic Pancreatitise

Abstract

Antibodies (Abs) to carbonic anhydrase (isoforms CA-I and CA-II) have been considered pathogenic factors in the development of autoimmune pancreatitis. Besides, such autoAbs might accelerate the pancreatic damage in alcoholic chronic pancreatitis (CP). The aim of the present study was to evaluate the presence of serum Abs to CA-I and CA-II in CP and the relative affinity of these Abs.Serum anti-CA-I and -CA-II Abs were measured in 89 patients with CP (48 alcoholic and 41 nonalcoholic) by an ELISA technique. The prevalence of those autoAbs in CP was compared with other autoimmune diseases where they have also been found. The presence of other serological manifestations of autoimmunity, such as hypergammaglobulinemia or antinuclear Abs, was determined in CP patients as well.Elevated serum levels of both anti-CA-I (24%) and -CA-II (18%) Abs were observed in CP, although their prevalence was lower than in autoimmune diseases like rheumatoid arthritis (44 and 25%, respectively) or systemic lupus erythematosus (39% for anti-CA-I Abs). Furthermore, these Abs were of low average avidity. On the other hand, a significantly higher proportion of nonalcoholic CP had anti-CA-II Abs with respect to alcoholic CP (15.2 vs. 2.4%, p < 0.05).Anti-CA-I and -CA-II Abs might be helpful in the diagnosis of autoimmune CP, and the detection of the latter Abs seems to discard alcoholic etiology. Although it does not discard any pathogenic role in autoimmune CP, the low-avidity of anti-CA Abs argues against such idea.

Serologic issues in IgG4-related systemic disease and autoimmune pancreatitis

“…Antibodies to carbonic anhydrase II (ACA II), the isotype characteristically present in pancreatic ductal epithelium [70] has been demonstrated with variable prevalence [60,69,[71][72][73][74][75] including one correlating it with serum IgG4 [45]. ACA II have also been demonstrated in other autoimmune diseases and hence are not specific for AIP [69].…”

“…ACA II have also been demonstrated in other autoimmune diseases and hence are not specific for AIP [69]. Antibodies to carbonic anhydrase I [69,72,73], carbonic anhydrase IV [76] and lactoferrin (ALA) [60] have also been reported. These serologic tests are not available in the US and their clinical utility is uncertain.…”

“…Their pathogenetic role is further strengthened by a similar distribution of organs involved by the disease and also by development of AIP in thymectomized mice immunized with carbonic anhydrase II or lactoferrin [77]. At the same time, other studies point against these possibilities [73][74][75]78]. Alpha Fodrin is another possible target antigen [79][80][81].…”

An Experimental Model of Autoimmune Pancreatitis in the Rat

“…Autoantibodies, such as antinuclear antibodies or antibodies directed against pancreatic enzymes such as carbonic anhydrase II (CA-II) or lactoferrin (LF), can also often be detected, further suggesting an autoimmune mechanism. 6 The rat has long served as a valuable model for the study of autoimmunity. Experimentally induced autoimmune diseases, such as experimental autoimmune encephalomyelitis, can be induced in rats by active immunization with proteins or peptides emulsified in adjuvants, or by adoptive transfer of activated T cells specific for autoantigenic determinants.…”