GS-IV 5 NUCLEAR LAMINA ANTIBODIES IN PRIMARY BILIARY CIRRHOSIS. F. Lozano, A. Par~s,, L. Borche, T. Gallart, and J. Rod@s Service of Immunology and Liver Unit. Hospital Clinic i Provincial. University of

Barcelona. Spain.

Antinuclear antibody (ANA) specific for nuclear membrane has recently been described in primary biliary cirrhosis (PBC), but there are no data about its antigenic specificity. The aims of this study were: l) to characterize the antigenic specificity of this new ANA-IFI pattern (ANLA), and 2} to assess the reliability of this antibody in PBC.

Identification of the nuclear membrane antigen was performed by Western blot analysis using nuclear matrix extract from mice liver, resistant to high salt conditions and non-denaturing detergents. The ANLA positive sera reacted with proteins which molecular weights (70 kD and 60 kD) correpond to the lamins A and C, two polypeptides of the nuclear lamina. This finding is also supported by an IFI study in which we appreciate the dissapearance of the nuclear lamina during spermatogenesis.

ANLA were tested in 40 patients with PBC and in a control group of 277 patients with other autoimmune ANA positive diseases. ANLA were present in 21 PBC patients (52.5%), but only in 2 patients in control group (0.7%) (p<O.O01). Furthermore, ANLA were present in 3 of the 4 PBC patients without mitoehondrial antibodies. Presence of ANLA in PBO was unrelated to the association with other autoimmune diseases, nor with the clinical and histologic stage of PBC.

In conclusion: l) in PBC there is an autoantibody that reacts specifically with components of the nuclear lamina, and 2) the high specifity of this new antibody in patients with primary biliary cirrhosis, suggests that it might be a new serological marker of the disease, particularly useful in those patients without AMA.

GS-[V 6 A PILOT DOUBLE BLIND CONTROLLED TRIAL OF PREDNISOLONE TREATMENT IN PRIMARY BILIARY CIRRHOSIS (PBC).

HC Mitchison, AJ Watson*, M_F Bassendine, CO Record, OFW James Departments of Medicine and Pathology% University of Newcastle Upon Tyne.

Despite the established benefit of steroid treatment in chronic active hepatitis no controlled trials of this treatment have been carried out in PBC.

18 pairs of patients (total 36) with established PBC (35 symptomatic or with portal hypertension) received either prednisolone 30 mg/day reducing to a maintenance of I0 mg/day over 2 months, or placebo. Pairs were matched for histological stage (11/18 in each group stage II or III, 7/18 cirrhotic), age~bilirubin. We present the results of clinical, histological, biochemical, and immunological findings after i year. There was marked improvements in pruritus and fatigue in the prednisolone treatment group, none in the placebo treated patients; i placebo patient died of liver failure. There were no treatment drop-outs.

PRED.MEAN AGE 54.1+8.9 SD MEAN INITIAL

% CHANGE VALUE + SEM

I lkaline Phos 759 iu/l + 87 -37 ilirubin 31.6 iu/l--~ 6 - 5.4 ST ]00 iu/l ~ 12.4 -11.7 ibumin 39.1 g/l ~ 0.94 + 3.9

~mmunoglobulin G 18.1 g/l + 1.72 -28.4 ~rocollagen III P 23 ng/ml ~ 2.4 -22.8 S ~ - ~ i t of prednisolone' treatment

PLACEBO.MEAN AGE 56.1+7.5 SD MEAN INITIAL VALUE + SEM 820 iuTl + 76 53.7 iu/l-~ 16.6 ]05 iu/l + 14.9 38.6 g/1 ¥ O.1 19.2 g /1 + 2.33 32.2 ng/m~ + 5.2 was seen i n - b i o c l

% CHANGE

- 5.8 +26.5 + 9.6 - 2.05 + 7 +6.6

emistry, IgG,

COMPARISON OF % CHANGE ACTIVE VS PLACEBO P< 0.01 P<0.1 P< 0.05 P<0.1 P< 0.05 P< 0.01 procollagen III

peptide. Significant (P=O.OI5) benefit was seen in 1 year histology.(piecemeal necrosis,inflam infi]trate, fibrosis). Adverse reactions: 2 prednisolone patients developed mild diabetes. We conclude: the marked symptomatic improvement and significant biochemical and histological benefit of prednisolone treatment strongly support the need for a larger longer study.

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