FTCD antigen

Details FTCD antigen FTCD antigen

1999-08-13

2001-10-09

Wortman, Donna C. (Department: 1648)

Chemistry: analytical and immunological testing

For preexisting immune complex or auto-immune disease

C436S518000, C436S820000, C435S007400, C435S007920, C435S007950, C536S023200, C536S023500

Reexamination Certificate

active

06300139

ABSTRACT:

BACKGROUND OF THE INVENTION
(a) Field of the Invention
The invention relates to formiminotransferase cyclodeaminase (FTCD) antigen which is liver specific to serve as a diagnostic tool for Autoimmune Hepatitis type II.
(b) Description of Prior Art
Autoimmune Hepatitis (AIH) is a disorder of unknown etiology responsible for a progressive destruction of the hepatic parenchyma with a high mortality if left untreated (Johnson P. J. et al., 1993,
Meeting Report: International Autoimmune Hepatitis Group, Hepatology,
18:998-1005). One of the characteristics of this disease is the presence of circulating autoantibodies in almost 90% of patients' sera. Clinical and serological differences between patients have lead to the classification of AIH into two types. Type 1 is characterized by the presence of anti-smooth muscle (SMA) and/or anti-nuclear antibodies (ANA) in patients' sera, while sera from Type II patients show anti-liver kidney microsomal antibodies type 1 (LKM1) (Homberg J. C. et al., 1987,
Hepatology,
7:1333-1339; Maggiore G. et al., 1993,
J. Pediatr. Gastroenterol Nutr.,
17:376-381). Recently, a new serological marker, anti-liver cytosol type I antibodies (LC1), was identified in 30% of patients with an AIH type II. In addition, LC1 proved to be the only serological marker in 10% of patients tested (Martini E. et al., 1988,
Hepatology,
8:1662-1666). This new organ specific autoantibody is a great contribution to the diagnosis of AIH, especially in patients considered so far as seronegative.
Recently, it was found that the liver cytosol recognized by LC1 had a molecular weight of 62 kDa in human liver and of 58 kDa in rat liver (Abuaf N. et al., 1992,
Hepatology,
16:892-898). Furthermore, the authors concluded that LC1 is a more specific marker of autoimmune hepatitis type II than the LKM1 (Abuaf N. et al., 1992,
Hepatology,
16:892-898).
It would be highly desirable to be provided with a diagnostic tool specific for Autoimmune Hepatitis type II.
SUMMARY OF THE INVENTION
One aim of the present invention is to provide a diagnostic tool specific for Autoimmune Hepatitis type II which would enable a clinician to distinguish AIH from HCV.
In accordance with the present invention there is provided the human liver FTCD as the specific antigen recognized by LC1 antibodies.
In accordance with the present invention there is provided a human liver specific FTCD antigen recognized by LC1 antibodies which essentially consists in the amino acid sequence of SEQ ID NOS:3 and 4 or variants thereof which are recognized by LC1 antibodies.
In accordance with the present invention there is provided such a human FTCD antigen which is encoded by a DNA sequence of SEQ ID NOS:1 and 2 and variants thereof which codes for an antigen recognized by LC1 antibodies.
In accordance with the present invention there is provided a method of diagnosis of Autoimmune Hepatitis (AIH) type II disease in a patient biological sample, which comprises the steps of:
a) subjecting a Western Blot having bound thereto an FTCD antigen of the present invention with the patient biological sample; and
b) detecting the presence of LC1 antibodies in the sample; whereby the presence of LC1 antibodies is indicative of AIH type II disease.
In accordance with the present invention there is provided an ELISA method of diagnosis of Autoimmune Hepatitis (AIH) type II disease in a patient biological sample, which comprises the steps of:
a) subjecting an ELISA plate having bound thereto an FTCD antigen of the present invention with the patient biological sample; and
b) detecting the presence of LC1 antibodies in the sample using rabbit anti-human IgG antibodies; whereby the presence of LC1 antibodies is indicative of AIH type II disease.
The term “variants thereof” is intended to mean any variation in the amino acid sequence of SEQ ID NOS:3 and 4 resulting in a peptide which is still recognized by LC1 antibodies or any variation in the DNA sequence of SEQ ID NOS:1 and 2 coding for a peptide which is still recognized by LC1 antibodies.
The term “molecular mimicry” is intended to mean any homology between the sequence of LCHCl and any other known sequence. LCHCl is a liver cytosol human clone 1 is the cDNA coding for human FTCD that we have identify in a cDNA library from HepG2 cells which codes for about 150 amino acids of the FTCD COOH-terminal region.


REFERENCES:
Murley et al., The Nucleotide Sequence of Porcine Formiminotransferase Cyclodeaminase, Expression and Purification fromEscherichia coli. The Journal of Biological Chemistry 268(30):22820-22824, 1993.*
Asuaf et al., Characterization of the Liver Cytosol Antigen Type 1 Reacting with Autoantibodies in Chronic Active Hepatitis. Hepatology 16(4):892-898, 1992.*
Solans et al., Cloning and characterization of human FTCD on 21q22.3, a candidate gene for glutamate formiminotransferase deficiency. Cytogenetics and Cell Genetics 88:43-49, 2000.

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