Humoral immune reaction in chronic liver diseases

In 60 patients with a morphologically ascertained chronic liver disease and 40 hepatologically examined patients with a healthy liver of a control group the quantitative determination of the immunoglobulin and the immunofluorescence-serological determination of antibodies against nuclei, smooth musculature and mitochondria were carried out. Only in one female patient with a chronic active hepatitis out of 51 patients with morphologically ascertained liver cirrhosis or chronic active hepatitis antibodies against nuclei and smooth musculature in a level of the titre of more than 1 : 40 and only in 2 female patients with a primary biliary cirrhosis antibodies against mitochondria could be proved in a level of the titre of more than 160. Titres of antibodies lying below were found in the group of patients with liver diseases and the control group in the same frequency, so that an autoimmune form of the cryptogenic cirrhosis could not be differentiated. The proof of antibodies against nuclei and smooth musculature of a high titre in connection with an isolated increase of the IgG is of special diagnostic importance for the autoimmune form of the chronic active hepatitis; the same is the case in the proof of antibodies against mitochondria of a high titre in connection with an isolated increase of IgM.     

Frequency and significance of antibodies to actin in type 1 autoimmune hepatitis

Antibodies to actin have been proposed as diagnostic markers for type 1 autoimmune hepatitis. Our aims were to determine 1) if testing for antibodies to actin is superior to testing for smooth muscle antibodies (SMA); 2) if these antibodies identify patients with distinctive clinical features; and 3) if the production of antibodies to actin is associated with genetic risk factors for autoimmune hepatitis. Sera from 99 patients with type 1 autoimmune hepatitis were tested. The frequencies of HLA B8, DR3, DR4, and A1-B8-DR3 in patient subsets were compared with those in 80 normal subjects. Seventy-three patients (74%) had antibodies to actin. Antibodies to actin were found more commonly in patients with SMA than in patients without them (86% vs. 7%, P < .0001). Screening only for antibodies to actin and antinuclear antibodies (ANA) failed to establish the diagnosis of autoimmune hepatitis in 5 patients. Patients with antibodies to actin were younger than seronegative patients. They were also more commonly DR3-positive than normal subjects and more frequently B8-positive than patients with non-actin-associated SMA (49% vs. 0%, P = .004). Only patients with antibodies to actin died of liver failure (6% vs. 0%), and 10 of 11 patients requiring liver transplantation were seropositive for these antibodies. Indeed, death and liver transplantation occurred more frequently in these patients than in actin-negative patients with ANA (19% vs. 0%, P = .03). We conclude that routine screening for antibodies to actin may miss patients with type 1 autoimmune hepatitis. Antibodies to actin are associated with HLA B8 and DR3, and they identify patients with a poor prognosis.     

A longitudinal study on the occurrence of autoantibodies in the course of acute hepatitis B

The presence or absence of autoantibodies in acute hepatitis B was investigated longitudinally in a prospective study of 38 patients, 37 of whom recovered completely. Antibodies to nuclei, bile canaliculi or mitochondria were not found in any of the 354 investigated sera. Smooth muscle antibody (SMA) was present in 23 patients for median 4 weeks and from (median) -1 to +3 weeks from peak SGPT. Titers reached from 1:10 to 1:400, with a median of 1:50. In the patient with persistent HBs-antigenemia, SMA - present in low titer (1:10) - persisted as well. Besides smooth muscle cells, other localisations were: glomerular (15 patients), around hepatocytes ('polygonal' 11 pts), around renal tubuli (10) and in the gastric mucosal layer (8). These fluorescence patterns, the presence of which was not correlated to the SMA titer height, disappeared either earlier than or simultaneously with smooth muscle cellular fluorescence. A maximal titer greater than 1:50 was associated with a thymol turbidity ten times the upper limit of normal or more (i.e. greater than 25 S-H U) and with the peak serumgammaglobulin about simultaneously with peak SGPT. The presence of SMA was not correlated with extrahepatic manifestations nor with the peak values attained for ESR, SGPT, alkaline phosphatase or bilirubin.     

Nanomolar quantification and identification of various nitrosothiols by high performance liquid chromatography coupled with flow reactors of metals and Griess reagent

To evaluate the histological findings in patients with chronic hepatitis C and autoimmune features, liver tissue specimens from 60 patients were graded under code for individual features and composite patterns that denoted autoimmune, viral, combined autoimmune and viral, and nondiscriminative changes. Portal, interface, and acinar hepatitis in any combination with plasma cell infiltration connoted an autoimmune pattern that was associated with higher serum levels of gamma-globulin (2.4 +/- 0.2 g/dL vs. 1.7 +/- 0.1 g/dL; P = .0003) and immunoglobulin G (2,211 +/- 227 mg/dL vs. 1,508 +/- 83 mg/dL; P = .001) than patients with other patterns. Patients with the autoimmune pattern also had a greater frequency of cirrhosis (43% vs. 8%; P = .003), higher mean Knodell score (13.2 +/- 0.9 vs. 6.8 +/- 0.9; P < .0001), and a greater occurrence of high-titer smooth muscle antibodies (SMA) (13% vs. 0%; P = .05) than patients with other histological findings. HLA DR3 also occurred more frequently in these individuals than in other patients (48% vs. 15%; P = .01) and normal subjects (43% vs. 16%; P = .01). Patients with nondiscriminative patterns and interface hepatitis had clinical findings similar to those with autoimmune patterns, except for a lower mean serum level of gamma-globulin. We conclude that the composite histological pattern that resembles autoimmune hepatitis is associated with greater immunoreactivity, inflammatory activity, and disease severity than other patterns. Interface hepatitis may be the most important histological finding associated with these clinical manifestations.     

On the experimental distinction between ssbs and dsbs in circular DNA

Positive serum anti-nuclear antibody (ANA) and anti-smooth muscle antibody (SMA) have been reported in 10-66% of patients with chronic hepatitis C virus (HCV) infection from Western countries. However, the mechanism involved in this immunological disorder is still unknown. This study was carried out to evaluate the prevalence and clinical significance of positive serum auto-antibodies in Chinese patients with chronic hepatitis C and to assess the role of serum HCV-RNA titre and HCV genotype in the presence of serum auto-antibodies. Serum ANA, SMA and anti-mitochondrial antibody (AMA) were measured in 122 patients with chronic hepatitis C. Clinical, biochemical and virological data (serum HCV-RNA titre and HCV genotype) were compared between patients with and without serum auto-antibodies. Fifty-eight (48%) patients were associated with positive serum auto-antibodies: 42 (34%) positive for ANA, six (5%) positive for SMA, nine (7%) positive for both ANA and SMA and one (1%) positive for AMA. Clinical parameters (age, sex, blood transfusion history), liver biochemical tests, the presence of cryoglobulinaemia or cirrhosis, and the response to interferon treatment were not significantly different between patients with and without positive serum auto-antibodies. Serum HCV-RNA levels and HCV genotypes were also not significantly different between the two groups. Logistic regression analysis showed that none of the previously mentioned parameters were significant predictors to associate with serum auto-antibodies in chronic hepatitis C. We concluded that 48% of Chinese patients with chronic hepatitis C were associated with positive serum auto-antibodies. Hepatitis C virus genotypes and serum HCV-RNA levels were not correlated to the presence of serum auto-antibodies. The clinical significance and actual pathogenesis of this phenomenon remain to be clarified.     

Serum autoantibodies in chronic hepatitis C: comparison with autoimmune hepatitis and impact on the disease profile

Antibodies to nuclei (ANA), smooth muscle (SMA), and liver/kidney microsomes type 1 (anti-LKM1) may occur in chronic hepatitis C. Distinct subspecificities, including ANA with the homogeneous pattern (ANA-H) and SMA with antiactin specificity (SMA-AA), are found in autoimmune hepatitis (AIH). This study was performed to characterize the hepatitis C virus (HCV)-associated autoantibodies and to evaluate their influence on the profile of the disease. Two hundred ninety consecutive patients with chronic hepatitis C and 35 control cases with AIH were screened for autoantibodies by indirect immunofluorescence (IFL) at 1:40 serum dilution. The ANA pattern was defined by IFL on HEp-2 cells and the SMA-AA identified by the presence of at least two of the following elements: 1) SMA(T) or SMA(G) pattern by IFL on kidney sections; 2) XR1 precipitating system by counterimmunoelectrophoresis; or 3) typical pattern by IFL on liver sections from phalloidin-intoxicated rats. ANA, SMA, and anti-LKM1 occurred in 9%, 20%, and 6% of chronic hepatitis C cases, respectively. The overall prevalence of autoantibodies was 30% (87 of 290). Compared with AIH, HCV-associated ANA and SMA exhibited ANA-H and SMA-AA at a lower prevalence (38% vs. 71%, P = .04 and 8% vs. 87%, P < .000001, respectively) and had a lower median titer (1:80 vs. 1:320, P < .001 and 1:40 vs. 1:320, P < .000001, respectively). The concomitant positivity for ANA-H and SMA-AA was detected in none of the HCV cases, but in 46% of AIH sera (P < .000001). Two parameters were independently associated with the autoantibodies in chronic hepatitis C: high alanine transaminase (ALT) serum levels (F = 14.04) and female gender (F = 5.03). At the univariate analysis, patients with autoantibodies had a more severe portal-periportal necroinflammation (median Scheuer's score: 2.05 vs. 1.64, P = .003). The presence of autoantibodies did not influence the response to interferon (IFN). In chronic hepatitis C, serum autoantibodies are common, but their subspecificities are distinct from those occurring in AIH. Whereas the absence of ANA-H and/or SMA-AA does not exclude AIH, the characterization of ANA and SMA may help to discriminate between the two conditions. As compared with the seronegative counterpart, autoantibody-positive chronic hepatitis C is more common in females and exhibits a more severe biochemical and histological activity. The response to IFN therapy, however, is similar.     

Fixation of human anti-actin autoantibodies on skeletal muscle fibres

Sera from five patients with chronic aggressive hepatitis containing smooth muscle autoantibodies were tested by means of indirect immunofluorescence for their binding to isolated rabbit skeletal muscle myofibrils. In all cases, the immunofluorescent staining was sharply localized to I bands. After incubation of these sera with skeletal muscle troponin-torpomyosin complex, purified troponin or purified tropomyosin, no changes in immunofluorescent staining of myofibrils were noted. However, the staining was abolished after incubation of the sera with skeletal muscle actin. In double immunodiffusion experiments, a single precipitation line was obtained after diffusion of the sera against crude or purified actin. It is concluded that, at least for the sera examined, smooth muscle autoantibodies are anti-actin autoantibodies. The high titre of such autoantibodies and their availability in clinical immunology laboratories make them a useful tool to study actin distribution in muscular and non-muscular cells.     

Studies of smooth-muscle antibodies in acute hepatitis

Smooth-muscle antibodies (SMA) of the IgG and IgM class in titres of 10 to 80 were demonstrated in 19 of 38 patients with acute hepatitis (50 per cent). No IgA-SMA were detected. IgM-SMA occurred in the beginning of the disease, while IgG-SMA were found both early and late in the course of disease. There was no correlation between the occurrence of SMA and the biochemical liver parameters or the mode of exposure to infection, but IgM-SMA were found more often in the first serum sample obtained from patients without hepatitis-B-associated antigen (HBAg) than in HBAg-positive patients (P1 + P2 = 0.04) and it is suggested that hepatitis virus A more readily than hepatitis virus B can elicit the formation of SMA. The mean PHA-induced lymphocyte-transformation response was significantly lower in hepatitis patients than in the controls (0.02 greater than p greater than 0.01). The lymphocyte-transformation response to a low PHA dose (1 mug per ml) was lower in hepatitis patients without SMA than in those with SMA (0.10 greater than p greater than 0.05). SMA were not found in 28 control persons, and the incidence of tissue antibodies other than SMA did not differ in hepatitis patients and controls.     

Characterization and structure of the mitochondrial small rRNA gene of the entomopathogenic fungus Beauveria bassiana

HCV infection and interferon-alpha (IFN-alpha) therapy have been associated with autoimmunity. To assess whether chronic liver disease (CLD) due to HCV infection or its treatment with IFN-alpha cause autoimmune manifestations, the prevalence of tissue autoantibodies in 51 children with chronic HCV infection and 84 with other CLD was analysed by standard techniques. Sixty-five percent of patients with chronic HCV infection, 66% with chronic hepatitis B infection and 60% with Wilson's disease were positive for at least one autoantibody. In the 51 subjects with chronic HCV infection (29 treated with IFN-alpha, 22 untreated), tested on 165 occasions over a median of 9 months (range 5-42 months), autoantibodies to nuclei (ANA), smooth muscle (SMA), gastric parietal cell (GPC) and/or liver kidney microsomal type 1 (LKM-1) were similarly prevalent in treated and untreated patients (90% versus 68%, P = 0.12). Positivity for SMA was present in 67%, GPC in 32%, ANA in 10%, LKM-1 in 8% of cases. Treatment with IFN-alpha had to be suspended due to transaminase elevation in one SMA-positive, one ANA-positive but in three of four LKM-1-positive patients. Our results show that: (i) autoantibodies are common in viral-induced hepatitis and Wilson's disease; (ii) positivity for SMA, GPC, ANA is part of the natural course of chronic HCV infection, their prevalence being unaffected by IFN-alpha; and (iii) IFN-alpha should be used cautiously in the treatment of LKM-1/HCV-positive patients.     

Antilactoferrin antibodies in autoimmune liver diseases

OBJECTIVE: Lactoferrin, an immunoregulatory protein in mucosal secretions, is one of the target antigens to perinuclear antineutrophil cytoplasmic antibodies (P-ANCAs). Circulating lactoferrin is cleared in the liver, but little is known about the implication of lactoferrin in hepatic inflammation. To evaluate the implication of immunological response to lactoferrin, we examined antilactoferrin antibodies in autoimmune liver diseases. METHODS: Fourteen patients with primary biliary cirrhosis (PBC), 14 with autoimmune hepatitis (AIH), five with autoimmune cholangitis (AIC), six with chronic hepatitis C, and five with chronic hepatitis B were studied. We evaluated autoantibodies to lactoferrin in the sera of the patients by the Western Immunoblotting method. RESULTS: Sera of five of the 14 patients (35.7%) with PBC, four of the 14 patients (28.6%) with AIH, and five of the five patients (100%) with AIC contained autoantibodies to human lactoferrin, but none with hepatitis B or C had them. The higher prevalence of serum antibodies to human lactoferrin was shown to be higher in patients with AIC than with hepatitis B (p < 0.01), hepatitis C (p < 0.01), PBC (p < 0.05), and AIH (p < 0.05). CONCLUSION: Lactoferrin located in bile ducts and liver cells is one of the candidates of target antigens in autoimmune liver diseases, especially in AIC.     

Mimicry between the hepatitis B virus DNA polymerase and the antigenic targets of nuclear and smooth muscle antibodies in chronic hepatitis B virus infection

Autoantibodies to nuclear and smooth muscle are common in hepatitis B virus (HBV) infection. To understand their origin, we scanned protein databases and found that HBV-DNA polymerase (HBV-pol) shares 7-9 amino acid sequences with nuclear (MHC II trans-activator, nuclear pore core protein, nuclear mitotic apparatus, and polymyositis sclerosis Ag) and smooth muscle proteins (caldesmon and myosin). Twenty-mer peptides with relevant homologues and an irrelevant control peptide were constructed and ELISAs were established. Sixty-five children with chronic HBV infection, 104 patients with other chronic liver diseases (CLD), 36 patients with extrahepatic autoimmune diseases, and 24 healthy controls were investigated. Double reactivity to HBV-pol peptides and corresponding self homologues was observed in 40% of HBV-positive patients as compared with four (4%) with other chronic liver diseases, two (6%) with extrahepatic autoimmune diseases, and in none of the healthy controls (p < 0.001 for all). Double reactivity to myosin or caldesmon peptides and their HBV-pol homologues was associated with anti-smooth muscle Ab positivity by immunofluorescence (p < 0.05 for both). HBV-positive sera double reactive for myosin or caldesmon and their homologous HBV-pol peptides also reacted with the native proteins on immunoblot. Fifty to ninety percent Ab inhibition to individual HBV-pol and HBV-pol99-118 peptides was noted by preincubation with individual HBV-pol/self homologue peptide and native proteins, respectively, but not with control peptide. Our results show that cross-reactive immunity targeting homologous sequences of viral and self proteins may partly account for autoantibody production in HBV infection.     

Electron microscopic observations on the elimination of the oocyte through the peritoneal epithelium in the neonatal mouse ovary

Six girls and one boy with cronic active hepatitis (CAH) of unknown etiology were between 9 and 15 years at the clinical onset of their illness. After beginning immunosuppressive therapy the course of their disease was followed from one to ten years. All had markedly increased IgG, high titres of smooth muscle antibodies (SMA) and antinuclear antibodies of IgG class in the earliest serum specimens tested. Therapy resulted in an improved sense of well-being and a decrease in SGOT, IgG and titres of SMA. Very high titres of measles antibodies were observed in all cases. In one of the cases CAH manifested itself after measles and in another after rubella infection. The first case in our series of patients died of liver failure after 5 years of illness. The other patients have survived and are able to live a normal life. The possibility of CAH should be considered when children develop symptoms of hepatitis. Longterm immunosuppressive treatment with regular clinical and laboratory evaluation is important. Estimation of titres of SMA is an additional parameter of value in following of the activity of CAH in these young patients.     

Cytochromes P450 and uridine triphosphate-glucuronosyltransferases: model autoantigens to study drug-induced, virus-induced, and autoimmune liver disease

Enzymes of phase I (cytochromes P450) and phase II (UDP [uridine diphosphate]-glucuronosyltransferases) of drug metabolism are targets of autoimmunity in the following chronic liver diseases of different etiology: 1)autoimmune hepatitis (AIH); 2) hepatitis associated with the autoimmune polyendocrine syndrome type 1 (APS-1); 3) virus-induced autoimmunity; and 4) drug-induced hepatitis. AIH is diagnosed by the following: the absence of infection with hepatitis viruses; the presence of a threshold of relevant factors, including circulating autoantibodies, hypergammaglobulinemia, female sex (female/male ratio 4:1), human leukocyte antigen (HLA) B8, DR3, or DR4; and benefit from immunosuppression. Patients with autoimmune hepatitis type 2 (AIH-2) are characterized by antibodies directed against liver and kidney microsomes, by an early onset of autoimmune hepatitis, which is a more aggressive course of the disease, and by a higher prevalence of autoimmunity directed against other organs. The major target of autoimmunity in patients with AIH-2 is cytochrome P450 2D6. Epitope mapping experiments revealed four short linear epitopes on cytochrome P450 2D6, recognized by liver/kidney microsomal autoantibodies type 1 (LKM-1) in patients with AIH-2. In addition, about 10% of the patient sera contain autoantibodies that detect a conformational epitope on UDP-glucuronosyltransferases (UGTs) of family 1. Presently, LKM-1 autoantibodies are used as diagnostic markers for AIH-2. It is unclear whether these autoantibodies have a pathogenetic role. Hepatitis is found in some patients with APS-1. Presumably this also is an autoimmune liver disease. APS-1 patients with hepatitis may develop autoantibodies directed against microsomal P450 enzymes of the liver; however, these autoantibodies do not recognize cytochrome P450 2D6, but they do recognize cytochrome P450 1A2. Autoimmunity in patients with APS-1 usually is directed against several organs simultaneously, and several organ specific autoantibodies may exist. Interestingly, APS-1 patients may produce various anti-cytochrome P450 antibodies. In addition to the hepatic anti-cytochrome P450, 1A2 autoantibodies are directed against steroidogenic cytochromes P450, namely P450 c21, P450 scc, and P450 c17. These autoantibodies correlate with adrenal and ovarian failure and often these steroidal cell autoantibodies precede the manifestation of adrenal or ovarian dysfunction. Whether anti-P450 1A2 autoantibodies have a similar predictive value is not yet known. LKM autoantibodies are further found in association with chronic hepatitis C and D. In chronic hepatitis C, the major target of LKM autoantibodies is cytochrome P450 2D6. Predominantly, conformational epitopes are recognized by LKM-1 sera of patients with chronic hepatitis C. In 13% of patients with chronic hepatitis D, LKM-3 autoantibody is detectable. The target proteins are UGTs of family 1 and in a minority of sera UGTs of family 2. The epitopes are conformational. All hepatic diseases discussed earlier have in common that autoimmunity, which is directed against enzymes of drug metabolizing multigene families. Each disease is characterized by a specific pattern of autoantibodies, with apparently little overlap. For example, LKM-1 autoantibodies, which are directed against P450 2D6, seem to overlap between AIH and chronic hepatitis C. However, a close examination of these autoantibodies shows differences between LKM-1 autoantibodies from patients with chronic hepatitis C and with AIH. In AIH, LKM autoantibodies are more homogenous, titers are higher, and major autoepitopes on cytochrome P450 2D6 are small and linear. LKM autoantibodies in viral hepatitis C are more heterogeneous and there are multiple epitopes, many of which are conformational. These differences indicate the different mechanisms that are involved in the generation of autoimmunity. (ABSTRACT TRUNCATED)     

Antibodies to soluble liver antigen, P450IID6, and mitochondrial complexes in chronic hepatitis

BACKGROUND: Antibodies to soluble liver antigen, P450IID6, and the E2 subunits of mitochondrial dehydrogenase complexes occur in autoimmune liver diseases, but their specificities and implications are uncertain. The aims of the present study were to assess the importance of these autoantibodies in different types of chronic hepatitis. METHODS: Sera from 62 patients with autoimmune hepatitis, 37 patients with cryptogenic hepatitis, and 19 patients with chronic hepatitis C were assessed under code by enzyme immunoassay. RESULTS: Antibodies to soluble liver antigen were found in 7 patients with autoimmune hepatitis (11%) and 5 patients with cryptogenic disease (14%). Patients with antibodies to soluble liver antigen were indistinguishable from seronegative counterparts with autoimmune hepatitis. Seropositive patients with cryptogenic hepatitis had autoimmune features, and they responded to corticosteroid therapy. Five patients (8%) with autoimmune hepatitis were seropositive for antibodies to mitochondrial complexes. Three lacked antimitochondrial antibodies. None of the patients had antibodies to P450IID6, and patients with chronic hepatitis C were seronegative for all markers. CONCLUSIONS: Antibodies to soluble liver antigen do not define a distinct subgroup of patients with autoimmune hepatitis. They may be found in some patients with corticosteroid-responsive cryptogenic hepatitis. Antibodies to E2 subunits and P450IID6 are uncommon in adults with chronic hepatitis.     

Frequency and significance of phenotypes for alpha1-antitrypsin deficiency in type 1 autoimmune hepatitis

To evaluate the frequency and significance of alpha1-antitrypsin deficiency in type 1 autoimmune hepatitis, 181 Caucasian patients were assessed for variant phenotypes. Three hundred three Caucasian patients with various other chronic liver diseases were similarly evaluated. Twenty-one of the 181 patients (12%) had heterozygous deficiencies, including the MS (6%) and MZ (6%) phenotypes. These patients were indistinguishable from those with normal phenotypes. Immediate outcomes after corticosteroid therapy were also similar in both groups. Variant phenotypes were present in 34 of the 303 patients with other chronic liver diseases (11%). Patients with nonalcoholic steatohepatitis had a significantly greater frequency of deficiency phenotypes than patients with chronic hepatitis C (20% vs 7%, P = 0.03). In conclusion, deficiency phenotypes are common in type 1 autoimmune hepatitis and they have no clinical or prognostic importance. In certain liver diseases, such as nonalcoholic steatohepatitis, variant phenotypes may be comorbid factors.     

Prenatal diagnosis of de novo interstitial 16q deletion in a fetus associated with sonographic findings of prominent coronal sutures, a prominent frontal bone, and shortening of the long bones

Ursodeoxycholic acid (UDCA) has been shown to have beneficial effects on patients with primary biliary cirrhosis, suggesting that UDCA has immunomodulating effects. We investigated the effect of UDCA in patients with autoimmune hepatitis (AIH) which is characterized by immunological abnormalities. Eight patients with type 1 AIH were treated with 600 mg of UDCA per day for 2 years. Based on the criteria of the International Autoimmune Hepatitis Group, five patients were diagnosed as definite and three as probable type 1 AIH. Liver function tests were performed every 4 weeks, before and during UDCA therapy and the serum levels of anti-nuclear antibodies (ANA), smooth muscle antibodies (SMA), immunoglobulin G and gamma globulin were determined every 3 months. The levels of serum aspartate aminotransferase and alanine aminotransferase significantly decreased from 154 +/- 24 IU/L and 170 +/- 17 IU/L before UDCA therapy to 31 +/- 3 IU/L and 25 +/- 5 IU/L (P < 0.001) after 1 year of treatment and 28 +/- 2 IU/L and 23 +/- 4 IU/L (P < 0.001) after 2 years of treatment. After 2 years of treatment, the levels of serum immunoglobulin G and gamma globulin significantly decreased (P < 0.05) and ANA titres (5/8 patients) were reduced and SMA (3/5 patients) became negative. Furthermore, hepatic histopathological changes of four patients were assessed after 1 year of treatment, and an improvement of intrahepatic inflammation, but not fibrosis, was observed. In conclusion, these results suggest that UDCA has a beneficial therapeutic effect in patients with type 1 autoimmune hepatitis.     

Detection of isotype-specific autoantibodies to calpastatin in sera from patients with rheumatic diseases using heat-treated HeLa cell extract as an antigen source for immunoblotting

To detect immunoglobulin isotype-specific autoantibodies to native human calpastatin in patients with rheumatic diseases, we performed immunoblot analysis using the heated HeLa cell extracts to enrich heat-resistant calpastatin. The calpastatin molecule that was apparently migrated to 110 kD by SDS-PAGE was confirmed to react with monoclonal anti-human calpastatin antibody in immunoblotting. IgG antibodies to calpastatin were detected in 22 of 48 sera (46%) from patients with RA, whereas only 20% (5/25), 11% (2/19) and 13% (2/15) of sera from SLE, SSc and PM/DM had IgG anti-calpastatin antibodies, respectively. IgM antibodies were also found in 40% (19/48) of RA and 12% (3/25) of SLE patients but not detected in sera from patients with other rheumatic diseases. IgA antibodies were found in only one RA and one SLE serum. In RA, 7 of 48 sera (15%) had IgM antibodies alone, but all SLE sera with IgM antibodies had IgG antibodies. Thus, anti-calpastatin autoantibodies were detected by using the native human calpastatin. Although these autoantibodies were found in patients with various rheumatic diseases, they were present in RA patients at the highest frequency. In particular, the presence of IgM antibodies appeared to be more specific in RA patients.     

Antinuclear antibodies and patterns of nuclear immunofluorescence in type 1 autoimmune hepatitis

To determine the significance of antinuclear antibodies and their patterns of indirect immunofluorescence in type 1 autoimmune hepatitis, sera from 99 patients were evaluated. Patients with antinuclear antibodies had a lower frequency of liver transplantation (6% vs 22%, P = 0.04) than seronegative patients. They were also more commonly HLA-DR4-positive than seronegative patients (56% vs 30%, P = 0.05) and normal subjects (56% vs 30%, P = 0.004). The 42 patients with antinuclear antibodies and a diffuse pattern of indirect immunofluorescence had higher serum titers of ANA (serum titers > or = 1:500, 71% vs 14%, P < 0.0001) and SMA (serum titers > or = 1:500, 69% vs 27%, P = 0.003) than the 22 patients with antinuclear antibodies and a speckled pattern. These patients, however, were otherwise not distinguished by clinical features and treatment response. Patients with a speckled pattern had A1-B8-DR3 more frequently than patients with a diffuse pattern (65% vs 23%, P = 0.005) and normal subjects (65% vs 13%, P < 0.0001), but they had no other salient features. We conclude that patients with antinuclear antibodies have a better long-term prognosis than seronegative patients, and they have HLA-DR4 more commonly. The patterns of indirect immunofluorescence associated with ANA positivity have no practical clinical implications.     

Antibodies to influenza A/swine-like viruses (Hsw1N1) in human sera: antigenic stimulation and changes in antibody status

Human sera collected at the end of 1975 were studied for HI antibodies to influenza A/Mayo Clinic/103/74 (Hsw1N1). The frequent occurrence of these antibodies in subjects born before 1930 suggested that they are present in about 25% of the Finnish population. During the H3N2 epidemic in winter 1975-76 a low response of antibodies to A/swine-like viruses was recorded in about half of the influenza patients with a pre-existing titre, but not in any of the patients without pre-existing antibodies. A comparison of samples collected in 1969 and 1975 suggested that at the community level the antibodies to A/swine-like viruses have not decreased during the era of the H3N2 subtype.