Evidence for a locally driven mucosal response and the presence of mitochondrial antigens in saliva in primary biliary cirrhosis

Sandra Reynoso-Paz, Patrick S Leung, Judith A Van de Water, Atsushi Tanaka, Santiago Munoz, Nathan Bass, Keith Lindor, Paul J. Donald, Ross L. Coppel, Aftab A. Ansari, M. Eric Gershwin

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Abstract

Primary biliary cirrhosis (PBC) is often considered to be a dry gland disease caused by frequent involvement of salivary and lacrimal glands. Although high titers of antimitochondrial autoantibodies (AMA) have long been recognized in PBC, little is known about the presence of mitochondrial autoantigens in mucosal compartments such as saliva. We investigated saliva and sera in PBC patients and controls for the presence of AMA and mitochondrial antigens. In PBC saliva, AMA were detected in 45 of 49 (92%), with specificity directed against pyruvate dehydrogenase complex (PDC-E2) alone in 22 of 49 (45%), against PDC-E2 and branched-chain 2-oxo-acid dehydrogenase complex E2 (BCOADC-E2) in 4 of 49 (8%), to PDC-E2 and 2- oxoglutarate dehydrogenase complex E2 (OGDC-E2) in 9 of 49 (18%), and to the 3 antigens together in 10 of 49 (20%). Isotyping of the saliva AMA showed that 80% of the patients had immunoglobulin A (IgA) against PDC-E2, 18% had IgM-specific PDC-E2, and 35% had IgG specific PDC-E2. Similar to serum and bile anti-PDC-E2 IgA antibodies, the saliva autoantibodies localized their reactivity to the inner lipoyl domain of PDC-E2. Furthermore, saliva from patients with PBC but not controls inhibited pyruvate dehydrogenase enzyme activity in vitro. In addition, and of particular interest, we detected a molecule with a molecular weight corresponding to PDC-E2 (74 kd) in PBC but not control saliva. These findings make several important points: first, there appears to be localized mucosal immunity in the secretory system of PBC; second, AMA are readily detected in PBC saliva; and third, PDC-E2 may be present in the saliva of PBC.

Original languageEnglish (US)
Pages (from-to)24-29
Number of pages6
JournalHepatology
Volume31
Issue number1
StatePublished - 2000

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Biliary Liver Cirrhosis
Saliva
Antigens
Autoantibodies
Immunoglobulin A
Dihydrolipoyllysine-Residue Acetyltransferase
3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
Ketoglutarate Dehydrogenase Complex
Lacrimal Apparatus
Mucosal Immunity
Autoantigens
Salivary Glands
Serum
Pyruvic Acid
Bile
Immunoglobulin M
Oxidoreductases
Immunoglobulin G
Molecular Weight
Antibodies

ASJC Scopus subject areas

  • Hepatology

Cite this

Evidence for a locally driven mucosal response and the presence of mitochondrial antigens in saliva in primary biliary cirrhosis. / Reynoso-Paz, Sandra; Leung, Patrick S; Van de Water, Judith A; Tanaka, Atsushi; Munoz, Santiago; Bass, Nathan; Lindor, Keith; Donald, Paul J.; Coppel, Ross L.; Ansari, Aftab A.; Gershwin, M. Eric.

In: Hepatology, Vol. 31, No. 1, 2000, p. 24-29.

Research output: Contribution to journalArticle

Reynoso-Paz, S, Leung, PS, Van de Water, JA, Tanaka, A, Munoz, S, Bass, N, Lindor, K, Donald, PJ, Coppel, RL, Ansari, AA & Gershwin, ME 2000, 'Evidence for a locally driven mucosal response and the presence of mitochondrial antigens in saliva in primary biliary cirrhosis', Hepatology, vol. 31, no. 1, pp. 24-29.
Reynoso-Paz, Sandra ; Leung, Patrick S ; Van de Water, Judith A ; Tanaka, Atsushi ; Munoz, Santiago ; Bass, Nathan ; Lindor, Keith ; Donald, Paul J. ; Coppel, Ross L. ; Ansari, Aftab A. ; Gershwin, M. Eric. / Evidence for a locally driven mucosal response and the presence of mitochondrial antigens in saliva in primary biliary cirrhosis. In: Hepatology. 2000 ; Vol. 31, No. 1. pp. 24-29.
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abstract = "Primary biliary cirrhosis (PBC) is often considered to be a dry gland disease caused by frequent involvement of salivary and lacrimal glands. Although high titers of antimitochondrial autoantibodies (AMA) have long been recognized in PBC, little is known about the presence of mitochondrial autoantigens in mucosal compartments such as saliva. We investigated saliva and sera in PBC patients and controls for the presence of AMA and mitochondrial antigens. In PBC saliva, AMA were detected in 45 of 49 (92{\%}), with specificity directed against pyruvate dehydrogenase complex (PDC-E2) alone in 22 of 49 (45{\%}), against PDC-E2 and branched-chain 2-oxo-acid dehydrogenase complex E2 (BCOADC-E2) in 4 of 49 (8{\%}), to PDC-E2 and 2- oxoglutarate dehydrogenase complex E2 (OGDC-E2) in 9 of 49 (18{\%}), and to the 3 antigens together in 10 of 49 (20{\%}). Isotyping of the saliva AMA showed that 80{\%} of the patients had immunoglobulin A (IgA) against PDC-E2, 18{\%} had IgM-specific PDC-E2, and 35{\%} had IgG specific PDC-E2. Similar to serum and bile anti-PDC-E2 IgA antibodies, the saliva autoantibodies localized their reactivity to the inner lipoyl domain of PDC-E2. Furthermore, saliva from patients with PBC but not controls inhibited pyruvate dehydrogenase enzyme activity in vitro. In addition, and of particular interest, we detected a molecule with a molecular weight corresponding to PDC-E2 (74 kd) in PBC but not control saliva. These findings make several important points: first, there appears to be localized mucosal immunity in the secretory system of PBC; second, AMA are readily detected in PBC saliva; and third, PDC-E2 may be present in the saliva of PBC.",
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T1 - Evidence for a locally driven mucosal response and the presence of mitochondrial antigens in saliva in primary biliary cirrhosis

AU - Reynoso-Paz, Sandra

AU - Leung, Patrick S

AU - Van de Water, Judith A

AU - Tanaka, Atsushi

AU - Munoz, Santiago

AU - Bass, Nathan

AU - Lindor, Keith

AU - Donald, Paul J.

AU - Coppel, Ross L.

AU - Ansari, Aftab A.

AU - Gershwin, M. Eric

PY - 2000

Y1 - 2000

N2 - Primary biliary cirrhosis (PBC) is often considered to be a dry gland disease caused by frequent involvement of salivary and lacrimal glands. Although high titers of antimitochondrial autoantibodies (AMA) have long been recognized in PBC, little is known about the presence of mitochondrial autoantigens in mucosal compartments such as saliva. We investigated saliva and sera in PBC patients and controls for the presence of AMA and mitochondrial antigens. In PBC saliva, AMA were detected in 45 of 49 (92%), with specificity directed against pyruvate dehydrogenase complex (PDC-E2) alone in 22 of 49 (45%), against PDC-E2 and branched-chain 2-oxo-acid dehydrogenase complex E2 (BCOADC-E2) in 4 of 49 (8%), to PDC-E2 and 2- oxoglutarate dehydrogenase complex E2 (OGDC-E2) in 9 of 49 (18%), and to the 3 antigens together in 10 of 49 (20%). Isotyping of the saliva AMA showed that 80% of the patients had immunoglobulin A (IgA) against PDC-E2, 18% had IgM-specific PDC-E2, and 35% had IgG specific PDC-E2. Similar to serum and bile anti-PDC-E2 IgA antibodies, the saliva autoantibodies localized their reactivity to the inner lipoyl domain of PDC-E2. Furthermore, saliva from patients with PBC but not controls inhibited pyruvate dehydrogenase enzyme activity in vitro. In addition, and of particular interest, we detected a molecule with a molecular weight corresponding to PDC-E2 (74 kd) in PBC but not control saliva. These findings make several important points: first, there appears to be localized mucosal immunity in the secretory system of PBC; second, AMA are readily detected in PBC saliva; and third, PDC-E2 may be present in the saliva of PBC.

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