A Novel Antibody Directed Against a Three‐Dimensional Configuration of a 95‐kDa Protein in Patients with Autoimmune Hepatic Diseases

Miyachi, Kiyomitsu; Miyata, Hiroshi; Hankins, Raleigh W.; Hirakata, Michito; Mimori, Tsuneyo; Hosaka, Hiroo; Amagasaki, Y; Miyakawa, Hiroshi; Kako, Makoto; Shibata, Minoru; Onozuka, Yasushi; Ueno, U.

doi:10.1046/j.1365-3083.1998.00262.x

Cited by 10 publications

(12 citation statements)

References 26 publications

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“…VCP plays a role in nuclear envelope assembly and the post-mitotic formation of the endoplasmic reticulum and Golgi apparatus. This antibody was found in 12% of patients with PBC [52], and was suggested to be associated with a milder course [19]. In general agreement with previous reports, our study found that antibodies to VCP were found in 11% of patients and the average Mayo risk score of the 12 patients positive for anti-VCP was 3·7 compared with 4·1 of the entire cohort.…”

Section: Discussionsupporting

confidence: 92%

Autoantibodies to GW bodies and other autoantigens in primary biliary cirrhosis

Stinton

Swain

Myers

et al. 2010

Clinical and Experimental Immunology

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SummaryAutoantibodies to intracellular targets in mitochondria and nuclei are serological hallmarks of primary biliary cirrhosis (PBC). One of the most recently identified cellular targets of PBC autoantibodies is a novel cytoplasmic structure referred to as GW bodies [GWB, G (glycine) W (tryptophan)-containing bodies (GWB)]. GWB are indentified as discrete cytoplasmic domains that are involved in mRNA processing via the RNA interference (RNAi) pathway. Key components of GWB include the proteins GW182, Ago2, RNA-associated protein 55 (RAP55) and Ge-1/Hedls. The primary objective was to study the frequency and clinical association of antibodies directed to GWB components, in 109 PBC patients. Autoantibodies to mitochondrial antigen-pyruvate dehydrogenase complex (M2), branched-chain 2-oxo-acid dehydrogenase complex and 2-oxo glutarate dehydrogenase complex (3E-BPO), gp210, sp100, promyelocytic leukaemia cell antigen (PML) and liver kidney microsomal-1 antigen (LKM-1) were detected by a line immunoassay and antibodies to GWB (GW182, RAP55, Ge-1, GW2, GW3) and glutamate receptor interacting protein (GRIP)-associated protein-1 (GRASP-1), by an addressable laser bead immunoassay (ALBIA). The most common GWB autoantigen targets were: RAP55-28%, GW182-12%, GW2-2% and antibodies to GRASP-1-17%. By comparison, the frequency of reactivity to established PBC autoantigens was: gp210, 27%; sp100, 27% and PML, 17%. None of the autoantibodies were associated with differences in Mayo risk score or liver decompensation. This study is the first study to show that antibodies to RAP55, GW182 and GRASP-1 are the most common GWB targets in PBC.

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Section: Discussionsupporting

confidence: 92%

Autoantibodies to GW bodies and other autoantigens in primary biliary cirrhosis

Stinton

Swain

Myers

et al. 2010

Clinical and Experimental Immunology

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“…Previously, we reported a novel antibody in autoimmune liver disease sera that reacted with a conformational epitope of a cytosolic 95 kDa protein, which we tentatively named p95c [14]. These antibodies were found in 12.5% of PBC and 9.8% of autoimmune hepatitis sera.…”

Section: Discussionmentioning

confidence: 99%

“…Subsequently, we studied a PBC serum and immunoprecipitated a cytosolic 95 kDa autoantigen (p95c) from HeLa cell lysates [13]. As the p95c autoantigen was not detected by immunoblot, we concluded that p95c was not identical to M9 and that anti‐p95c antibodies reacted with a conformational epitope of the cognate cytosolic antigen [14].…”

Section: Introductionmentioning

confidence: 99%

“…Immunoassays: immunodiffusion, immunoprecipitation and addressable laser bead immunoassay. The Ouchterlony double immunodiffusion method was used to screen for anti‐p97/VCP antibodies [13, 14, 18]. Briefly, the prototype serum and 20 mg of rabbit thymus extract or rat liver supernatant were used as antigen source to detect autoantibodies as previously described [13, 14, 18].…”

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confidence: 99%

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Anti‐p97/VCP Antibodies: An Autoantibody Marker for a Subset of Primary Biliary Cirrhosis Patients with Milder Disease?

Miyachi¹,

Hosaka

Nakamura

et al. 2006

Scand J Immunol

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We previously reported that 12.5% of primary biliary cirrhosis (PBC) sera reacted with a 95 kDa cytosol protein (p95c) that was subsequently identified as a p97/valosin-containing protein (VCP). The clinical features and course of the six anti-p97/VCP-positive PBC patients with Scheuer's stage 1 and 2 liver biopsies were monitored for an average of 15 years. This group was compared with 50 PBC patients that did not have detectable anti-VCP. Autoantibodies to a full-length recombinant p97/VCP were assayed by immunoprecipitation. All six PBC patients with anti-VCP had antibodies to the mitochondrial pyruvate dehydrogenase complex-E2 antigen as measured by an addressable laser bead immunoassay. The first was a male with no evidence of liver failure that died of cerebral infarction at the age of 85. The second was a 73-year-old female with Hashimoto's thyroiditis who has remained clinically stable without ursodeoxycolic acid (UDCA) treatment. Although the third had no HCV antibodies, he developed hepatocellular carcinoma at the age of 76 and died of renal failure at 78. The fourth was a 50-year-old female who remained clinically stable during follow-up and the fifth with Hashimoto's thyroiditis and stable liver function following UCDA treatment. The sixth was a male patient presenting a mild clinical course. The clinical course of these patients was in contrast to the 50 comparison group PBC patients who did not have anti-p97/VCP. As the six PBC patients with anti-p97/VCP antibodies had slowly progressive liver disease and no mortality related to autoimmune liver disease, our observations suggest that this autoantibody might be an indicator of a favourable prognosis.

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“…12 Anti-SS-A/Ro, SS-B/La, U1RNP, Sm, Scl 70, Ki, Ku, rRNP, Wa and p95c/p97/VCP were screened by double immunodiffusion. 13 Anti-SS-A/Ro, SS-B/La, U1RNP, Sm, Scl 70 (Topo-isomerase 1), and anti-mitochondrial antibodies were further confi rmed by enzyme-liked immunosorbent assay using commercial kits. Immunoprecipitation was used for the confi rmation of anti-Ki, Ku, 14 rRNP, Wa, 15 WS, 16 and p97/VCP.…”

Section: Detection Of Autoantibodiesmentioning

confidence: 99%

Inositol 1,4,5-trisphosphate receptors are autoantibody target antigens in patients with Sjögren's syndrome and other systemic rheumatic diseases

Miyachi¹,

Iwai

Asada

et al. 2007

Mod Rheumatol

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IP(3)R2 and IP(3)R3 double knock-out mice present with exocrine dysfunctions such as secretion deficits of saliva and pancreatic juice. Therefore, we investigated whether the presence of antibodies to IP(3)Rs could be found in patients with Sjögren's syndrome, and the location of the epitopes. Subjects included 35 primary Sjögren's syndrome, 39 secondary Sjögren's syndrome, 144 rheumatoid arthritis, and 96 other connective tissue disease patients. As controls, 33 healthy subjects were included. Immunoblot was conducted using recombinant proteins IP(3)R1, IP(3)R2, and IP(3)R3 made from full-length cDNA, and core, T604, and EL for epitope mapping. Antibodies to IP(3)R1 in sera from patients with primary Sjögren's syndrome, secondary Sjögren's syndrome, and rheumatoid arthritis were found to be positive in 17 of 35 (48.6%), 13 of 39 (33%), and 34 of 124 (27.4%) cases, respectively. These frequencies were significantly higher than the 1 of 33 (3.0%) found in normal healthy subjects. The frequency of anti-IP(3)R2 antibodies in rheumatoid arthritis was found to be higher than those found in Sjögren's syndrome, systemic lupus erythematosus, and systemic sclerosis. Anti-IP(3)R2 antibodies found in rheumatoid arthritis primarily recognized residues 578-2171 of the internal coupling and regulatory domain. On the other hand, anti-IP(3)R1 found in Sjögren's syndrome recognized residues 224-604 of the core protein IP(3)R1. Anti-IP(3)R1 antibodies were present in 48.6% of primary Sjögren's syndrome and in 3.0% of normal healthy subjects. Anti-IP(3)R2 antibodies were detected most frequently in rheumatoid arthritis. Locations of the antigenic epitopes were found to differ among the disease conditions.

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A Novel Antibody Directed Against a Three‐Dimensional Configuration of a 95‐kDa Protein in Patients with Autoimmune Hepatic Diseases

Cited by 10 publications

References 26 publications

Autoantibodies to GW bodies and other autoantigens in primary biliary cirrhosis

Autoantibodies to GW bodies and other autoantigens in primary biliary cirrhosis

Anti‐p97/VCP Antibodies: An Autoantibody Marker for a Subset of Primary Biliary Cirrhosis Patients with Milder Disease?

Inositol 1,4,5-trisphosphate receptors are autoantibody target antigens in patients with Sjögren's syndrome and other systemic rheumatic diseases

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