Increased Serum Terminal Complements Complex Levels in Attention Deficit Hyperactivity Disorder Children.

Background: Attention deficit hyperactivity disorder (ADHD) is a widespread neuropsychiatric disorder in both children and adolescents, which is associated with social isolation and poor academic performance. Complement proteins are regarded as a major player in inflammation and disease development for several neuropsychiatric diseases such as schizophrenia and bipolar diseases. As clarified by previous data, increased levels of complement molecules and other immunological markers as cytokines were demonstrated in these disorders. Limited studies have investigated complement proteins particularly terminal complement complex or membrane attack complex (C5b-9) among ADHD patients. The present research aims to elucidate the association between C5b-9 complex protein and ADHD. Methods: This is a cross-sectional study. Sera were collected from Al-Hussain Teaching Medical City in Holy Karbala, Iraq, during 2019-2020. Sera were tested for C5-b9 using commercial kits by enzyme-linked immunosorbent assay (ELISA). Results: In 90 participants included in the study, a significant increment in C5b-9 levels among ADHD patients (P=0.019) was observed. Patients with positive C5b-9 levels had a 2.76 times higher risk of developing ADHD than control subjects. The diagnostic utility for C5b-9 was statistically significant with 71.11% sensitivity, 55.6% specificity, and a high negative predictive value (97.3%). Conclusion: The study concluded elevation of the C5b-9 terminal complements complex levels in ADHD patients, which could point to the association of complement proteins as inflammatory markers with the ADHD disease process.

Alcohol dehydrogenase-specific T-cell responses are associated with alcohol consumption in patients with alcohol-related cirrhosis.

UNLABELLED: Patients with alcohol-related liver disease (ALD) have antibodies directed to alcohol dehydrogenase (ADH), anti-ADH titers being associated with disease severity and active alcohol consumption. ADH-specific T-cell responses have not been characterized. We aimed to define anti-ADH cellular immune responses and their association with active alcohol consumption and disease severity. Using cultures of peripheral blood mononuclear cells (PBMCs) from 25 patients with alcohol-related cirrhosis (ARC; 12 were actively drinking or abstinent for <6 months, and 13 were abstinent for >6 months) and hepatic mononuclear cells (HMCs) from 14 patients with ARC who were undergoing transplantation, we investigated T-cell reactivity to 25 overlapping peptides representing the full human ADH protein (beta 1 subunit). ADH-specific peripheral T-cell responses were assessed by the quantification of T-cell proliferation and cytokine production and were correlated with the clinical course. In active alcohol consumers, proliferative T-cell responses targeted ADH31-95 and other discontinuous sequences in the ADH peptide, whereas only one sequence was targeted in abstinents. ADH peptides induced the production of interferon-γ (IFN-γ), interleukin-4 (IL-4), and IL-17. IL-4 production was lower in active drinkers versus abstinents, and IL-17 production was higher. Peptides inducing IFN-γ production outnumbered those inducing T-cell proliferation. The intensity of the predominantly T helper 1 (Th 1) responses directly correlated with disease severity. Similar to PBMCs in abstinents, ADH peptides induced weak T-cell proliferation and a similar level of IL-4 production in HMCs but less vigorous Th 1 and T helper 17 responses. CONCLUSION: This suggests that Th 1 responses to ADH in ARC are induced by alcohol consumption. A Th 1/T helper 2 imbalance characterizes T-cell responses in active drinkers with ARC, whereas IL-4 production prevails in abstinents. This identifies new targets for immunoregulatory therapies in ALD patients for halting detrimental effector T-cell responses, which may encourage liver fibrogenesis and progression to end-stage liver disease.

Immunohistochemical phenotyping of the inflammatory infiltrate in de novo autoimmune hepatitis after liver transplantation in children.

We have investigated the inflammatory infiltrate in post-transplant dn-AIH, a form of late insidious graft rejection, focusing on transcription factors defining effector and T-regs, using an antigen retrieval immunohistochemical method on archived liver tissue, and compared it with ACR and classical AIH. Paraffin-embedded liver biopsies from pediatric patients with dn-AIH (n = 10), ACR (n = 10), and AIH (n = 13) were selected randomly and stained using antibodies directed to CD4, CD8, T-bet (marker of Th1 polarization), GATA-3 (marker of Th2 polarization), FOXP3 (marker for T regulatory cells), IL-17, CD56 (NK cells), and perforin. Portal and lobular lymphocytic infiltrate was assessed semi-quantitatively. Prominent CD4, CD8, and T-bet positivity were present in both the lobular and portal infiltrate of all three conditions. Overall T-bet score of lobular inflammation in the dn-AIH group was lower than in the ACR and AIH groups (p = 0.02). In contrast, most samples showed absent or minimal GATA-3 positivity. FOXP3, CD56, IL-17, and perforin staining of mild to moderate severity were present in all three groups in both the portal and lobular infiltrate. A Th1 polarization of the inflammatory infiltrate characterizes dn-AIH, but also ACR and AIH.

Cytokine levels and profiles in children related to sickle cell disease and asthma status.

Atopic asthma in patients with sickle cell disease (SCD) is associated with an increased risk of acute chest syndrome (ACS). Cytokine-mediated inflammation might explain this association. Studies of cytokine profiles in patients with SCD have yielded conflicting data, but the possible influence of asthma status has not been examined. Our aim was to test the hypothesis that cytokine levels and profiles in SCD children reflected their asthma status. Samples from 155 Jamaican children (80 had SCD) and 64 British children (53 had SCD) who had their asthma status documented were analyzed for the presence and levels of interleukin 4 (IL-4) and interferon (IFN)-γ; they were also classified by their T helper cell (Th) cytokine profile. Jamaican children with SCD, when compared with Jamaican controls, were more likely to be diagnosed with asthma (P=0.001), more likely to be IL-4 positive (P<0.001), and more likely to be classified as having a Th-2 pattern (<0.001). In contrast, British children with SCD, when compared with the British controls, were less likely to have been diagnosed with asthma (P=0.04) and less likely to be classified as having a Th-2 pattern (P=0.006). Regression analysis demonstrated that amongst Jamaican children, SCD status, but not asthma status, ACS history, or gender, was predictive of IL-4 positivity and Th-2 status (P<0.001). In British children, none of those variables were significant predictors of IL-4 positivity or Th status. Cytokine profiles differed between Jamaican and British children. In the Jamaican children they reflected SCD, but not asthma or ACS status.

Autoantigen-specific regulatory T cells, a potential tool for immune-tolerance reconstitution in type-2 autoimmune hepatitis.

UNLABELLED: Effector CD4 and CD8 T cell immune responses to cytochrome P450IID6 (CYP2D6), the autoantigen of autoimmune hepatitis type 2 (AIH-2), are permitted by a numerical and functional impairment of CD4(pos) CD25(high) regulatory T cells (T-regs). We aimed to investigate whether T-regs specific for CYP2D6 immunodominant regions and restricted by the appropriate human leukocyte antigen (HLA)-DR molecule can be generated in patients with AIH-2 and can control CD4 and CD8 T cell effectors targeting identical or overlapping CYP2D6 regions. CYP2D6-specific regulatory T cells (CYP2D6 T-regs) were obtained from peptide-pulsed monocyte-depleted peripheral blood mononuclear cells of 17 patients with AIH-2, who were positive for the predisposing HLA-DR7 and/or HLA-DR3 alleles. Their antigen specificity was assessed by cytofluorimetry using HLA class II tetramers and their cytokine profile by intracellular staining. T-reg ability to suppress was ascertained by measuring reduction of CD4(pos) CD25(neg) cell proliferation/effector cytokine secretion and of CD8 T cell cytotoxicity. The most efficient suppression of effector T cell proliferation, inflammatory cytokine release, and cytotoxicity was obtained by coculturing T-regs with CYP2D6-peptide-loaded semimature dendritic cells (smDCs), and smDC-CYP2D6 T-regs also expressed high levels of FOXP3 (forkhead box P3). Possession of the appropriate HLA-DR molecule and recognition of the CYP2D6 autoantigenic sequence were critical to the synergistic smDC-CYP2D6 T-reg immunoregulatory functions, and lack of either element led to poor control of responder cell proliferation and cytokine secretion. Moreover, interferon-γ neutralization significantly boosted the suppressive ability of CYP2D6 T-regs. CONCLUSION: T-regs generated under CYP2D6-specific conditions and cocultured with smDCs are highly effective at controlling autoreactive T cells, thus providing the basis for a powerful and tailored form of immunotherapy for AIH-2.

Severity of the compensatory anti-inflammatory response determined by monocyte HLA-DR expression may assist outcome prediction in cirrhosis.

PURPOSE: To investigate variations in expression of the monocyte antigen presentation molecule HLA-DR in cirrhosis. METHODS: HLA-DR expression was measured by flow cytometry in 100 patients within 48 h of admission and repeated a week later in 21 patients admitted to ICU. IL-10, TNF-α and IFN-γ secretion in response to lipopolysaccharide and recall antigens were measured by enzyme-linked immunosorbent spot (ELISPOT) assay in 12 patients (7 with clinical immunoparesis, 5 stable). RESULTS: HLA-DR level was 71% in stable patients, 53% with single organ dysfunction and 34% with multiple organ failure (p < 0.02). Within these groups, no significant differences in admission HLA-DR were seen between survivors and non-survivors. HLA-DR expression less than 40% predicted 90-day mortality with a specificity of 80% and sensitivity of 59% [area under the receiver operator curve (AUROC) 0.76]. HLA-DR less than 40% was an independent predictor of prognosis in multivariate analysis with a relative risk of 2.35 (p = 0.04), although sequential organ failure assessment score (SOFA) score displaced HLA-DR when included. In those admitted to intensive care failure to increase HLA-DR expression was predictive of death within 30 days (risk ratio 6.9, p = 0.007). Follow-up values predicted outcome with similar accuracy to acute physiology and chronic health evaluation II (APACHE II)/SOFA scores (AUROC 0.88). Response to endotoxin and recall antigen was characterised by an anti-inflammatory cytokine secretion profile, and was associated with impairment in recall antigen presentation capacity. CONCLUSIONS: HLA-DR expression less than 40% and a failure of recovery predict poor outcome in decompensated cirrhosis, but overall prognostic power remains inferior to conventional markers. Ex vivo experiments demonstrate reduced Th1 response to antigenic stimulation and an exaggerated counter-inflammatory cytokine secretion profile.

Serum levels of CK18 M30 and leptin are useful predictors of steatohepatitis and fibrosis in paediatric NAFLD.

BACKGROUND: With the alarming growth in prevalence of paediatric nonalcoholic fatty liver disease (NAFLD), there is a need for noninvasive methods of stratifying disease severity. Our aim was to evaluate a combination of serum biomarkers as a measure of disease activity in paediatric NAFLD. PATIENTS AND METHODS: Forty-five children with biopsy-proven NAFLD were enrolled. Caspase-cleaved CK18 fragments (CK18 M30), hyaluronic acid, leptin, and adiponectin were measured in serum using enzyme-linked immunosorbent assays and high-sensitivity C-reactive protein using a colorimetric assay. RESULTS: Median age was 12.7 years (55% boys). Median body mass index z score was 1.7. CK18 M30 levels were significantly higher in patients with NAFLD versus controls, median 288 IU/L versus 172 IU/L (P < 0.001), and in those with steatohepatitis, median 347 IU/L versus simple steatosis (NAFLD activity score < 3), median 191 IU/L (P = 0.006). Significant fibrosis (≥F2) could be differentiated from no/minimal fibrosis (

A multifaceted imbalance of T cells with regulatory function characterizes type 1 autoimmune hepatitis.

UNLABELLED: Immunotolerance is maintained by regulatory T cells (Tregs), including CD4(+)CD25(hi), CD8(+)CD28(-), gammadelta, and CD3(+)CD56(+) [natural killer T (NKT)] cells. CD4(+)CD25(hi) cells are impaired in children with autoimmune hepatitis (AIH). Little is known about Tregs in adults with AIH. The aim of this study was to investigate the frequency and function of Treg subsets in adult patients with AIH during periods of active disease and remission. Forty-seven AIH patients (16 with active disease and 31 in remission) and 28 healthy controls were studied. Flow cytometry was used to evaluate surface markers and function-related intracellular molecules in gammadelta, CD8(+)CD28(-), NKT, and CD4(+)CD25(hi) cells. CD4(+)CD25(hi) T cell function was determined by the ability to suppress proliferation and interferon gamma (IFN-gamma) production by CD4(+)CD25(-) target cells. Liver forkhead box P3-positive (FOXP3(+)) cells were sought by immunohistochemistry. In AIH patients, particularly during active disease, CD4(+)CD25(hi) T cells were fewer, expressed lower levels of FOXP3, and were less effective at inhibiting target cell proliferation versus healthy controls. Moreover, although the numbers of CD8(+)CD28(-) T cells were similar in AIH patients and healthy controls, NKT cells were numerically reduced, especially during active disease, and produced lower quantities of the immunoregulatory cytokine interleukin-4 versus controls. In contrast, gammadelta T cells in AIH patients were more numerous versus healthy controls and had an inverted Vdelta1/Vdelta2 ratio and higher IFN-gamma and granzyme B production; the latter was correlated to biochemical indices of liver damage. There were few FOXP3(+) cells within the portal tract inflammatory infiltrate. CONCLUSION: Our data show that the defect in immunoregulation in adult AIH is complex, and gammadelta T cells are likely to be effectors of liver damage.

Vigorous activation of monocytes in juvenile autoimmune liver disease escapes the control of regulatory T-cells.

UNLABELLED: Interface hepatitis, the histological lesion typical of autoimmune hepatitis (AIH), is composed of CD4 and CD8 T lymphocytes and of innate immunity cells, particularly monocytes. Studies in AIH have focused on autoreactive CD4 and CD8 T cells and impairment of CD4+CD25+ regulatory T cells (T-regs), whereas little is known about the role of monocytes and their relationship with T-regs. We have investigated 51 patients with autoimmune liver disease (AILD) and 27 healthy subjects, finding that monocytes were higher in number (P = 0.044), had a more vigorous spontaneous migration (P < 0.0005 in patients with inactive disease [ID], and P < 0.001 in those with active disease [AD]), displayed a higher tumor necrosis factor alpha (TNF-alpha) over interleukin (IL)-10 production (P = 0.07 in ID and P = 0.0005 in AD), and expressed higher levels of Toll-like receptor (TLR) 4 (P = 0.048 in ID and P = 0.03 in AD). Addition of conventional T-regs (cT-regs) in AILD enhanced monocyte migration (P = 0.05 in ID and P = 0.08 in AD), magnified TNF-alpha over IL-10 production (P = 0.0005 in ID and P = 0.006 in AD), and markedly increased TLR4 expression levels (P = 0.01 in ID and P = 0.004 in AD), whereas in normal subjects it either restrained or left unchanged monocyte function. Because a CD127-negative subpopulation within CD4+CD25+ T cells exerts the strongest regulatory activity, we performed additional experiments using purified CD4+CD25+CD127- T cells (true T-regs [tT-regs]). Addition of tT-regs to monocytes decreased monocyte migration (P = 0.03) and promoted IL-10 production (P = 0.009), leaving unchanged TLR4 expression in healthy subjects, whereas in patients with AILD it induced only a marginal increase in IL-10 production (P = 0.045 in ID and P = 0.13 in AD). CONCLUSION: Monocyte overactivation and inability of cT-regs and tT-regs to restrain it may contribute to the loss of immune tolerance and perpetuation of the autoimmune attack in AILD.

The increasing prevalence of hepatitis delta virus (HDV) infection in South London.

On the basis of historical studies, hepatitis delta virus (HDV) infection is considered uncommon in the United Kingdom (UK) and mainly confined to intravenous drug users. In order to assess the current prevalence of HDV co-infection in patients with chronic hepatitis B (HBV), a retrospective analysis was performed of 962 consecutive HBV-infected adult patients referred to King's College Hospital between January 1st 2000 and March 31st 2006. The 82 subjects positive for HDV antibody (8.5%) had a similar age to those without HDV (median 36 years, interquartile range 30-47, vs. 35 years, 29-43). Excluding non-UK residents, the prevalence of HDV Antibody was 7.1%. Most HDV-infected subjects were born in regions where HDV is endemic, for example, Southern or Eastern Europe (28.1%), Africa (26.8%) or Middle-East (7.3%). Forty one (50%) were considered to have acquired HDV infection via intra-familial transmission but intravenous drug use was still a common route of transmission (24.4%). Comparing HBV/HDV co-infected to HBV mono-infected patients, a higher proportion were hepatitis C antibody positive (25.6% versus 3.8%; odds ratio 8.89, 95% confidence interval 4.4-17.9; P < 0.00001) and more had cirrhosis (26.8% vs. 12.9%; odds ratio 2.64, 95% confidence interval 1.55-4.49; P < 0.0001) but, despite this, the risk of hepatocellular carcinoma was similar (odds ratio 1.34, 95% confidence interval 0.62-2.91). Although HDV infection is reportedly declining in some endemic regions, our data demonstrate a high prevalence in South London. HDV co-infection is associated with increased morbidity and patients with HBV should be tested for HDV infection.

Actin-free Gc globulin: a rapidly assessed biomarker of organ dysfunction in acute liver failure and cirrhosis.

Reductions in serum levels of Gc globulin, a hepatically synthesized component of the extracellular actin scavenger system responsible for complexing circulating actin and attenuating intravascular microthrombus formation, are associated with poor outcome in acute liver failure. Clinically applicable assays of the important actin-free fraction (Af-Gc) have not been available until now. We measured actin-free Gc globulin levels with a novel, rapid assay in 61 cases of acute liver failure (ALF) and in 91 patients with cirrhosis (40 of whom were clinically unstable with extrahepatic organ dysfunction), and studied associations with liver dysfunction, extrahepatic organ dysfunction, indices of disseminated coagulation, and outcome. Reductions in Af-Gc levels mirrored hepatic dysfunction and organ dysfunction in both groups, and discriminated patients with poor prognosis from those with good prognosis in the ALF cohort. Levels were lowest in patients with ALF (10% of control values), but levels were also markedly reduced in both unstable (28%) and stable (44%) patients with cirrhosis. Associations with markers of disseminated intravascular coagulation were seen in both groups, most notably in the cirrhosis cohort, supporting a pathophysiological role for reduced Af-Gc in the evolution of organ dysfunction. In acetaminophen-induced ALF, Af-Gc identified patients with poor prognosis as well as did the Acute Physiology and Chronic Health Evaluation (APACHE II) score (area under the receiver operating characteristic curve, 0.7), and in cirrhosis, Af-Gc was an independent predictor of mortality by multifactorial analysis. In conclusion, the importance of Af-Gc reductions in the development of multiple organ dysfunction in ALF and cirrhosis is highlighted, probably resulting from reduced hepatic production and peripheral exhaustion of this arm of the extracellular actin scavenger system.

Cytochrome P450IID6-specific CD8 T cell immune responses mirror disease activity in autoimmune hepatitis type 2.

UNLABELLED: Autoimmune hepatitis type 2 (AIH-2) is a severe organ-specific disorder characterized by liver kidney microsomal antibody type 1 targeting cytochrome P4502D6 (CYP2D6). Growing evidence implicates the involvement of CD8 T cell immune responses in its pathogenesis. We investigated CYP2D6-specific CD8 T cell human leukocyte antigen (HLA)-A2 restricted responses in AIH-2 (20 patients, 11 HLA-A2+). Binding affinity of CYP2D6 peptides to HLA-A2 was predicted by the algorithm SYFPEITHI and assessed in vivo by T2 cell assays. CD8 T cell interferon (IFN)-gamma production was assessed via intracellular cytokine staining, cytotoxicity via chromium release assay, and frequency of circulating and intrahepatic CYP2D6-specific CD8 T cells via tetramer staining. CYP2D6-specific CD8 T cell reactivity was tested at diagnosis and during treatment and correlated with indices of disease activity. Seven CYP2D6 peptides with high HLA-A2 binding affinity colocalizing with known B cell or CD4 T cell epitopes were selected. Five sequences inducing high levels of IFN-gamma were used for HLA-A2 tetramer construction. Frequency, IFN-gamma production, and cytotoxicity of CYP2D6-specific CD8 T cells were higher at diagnosis than during treatment. Intensity of CYP2D6-specific CD8 T cell responses correlated with disease activity. Immune responses to CYP2D6(245-254) were the strongest both at diagnosis and during treatment. CONCLUSION: HLA-A2-restricted, CYP2D6-specific CD8 T cell immune responses vary according to disease stage and correlate with hepatocyte damage. CD8 T cell targets on CYP2D6-in particular CYP2D6(245-254)-may be the focus of novel immune intervention in AIH-2. (HEPATOLOGY 2007.).

Functional study of CD4+CD25+ regulatory T cells in health and autoimmune hepatitis.

Regulatory CD4(+)CD25(+) T cells (Tregs) are defective numerically and functionally in autoimmune hepatitis (AIH). We have investigated and compared the mechanism of action of Tregs in healthy subjects and in AIH patients using Transwell experiments, where Tregs are cultured either in direct contact with or separated from their targets by a semipermeable membrane. We also studied Treg FOXP3 expression and effect on apoptosis. Direct contact is necessary for Tregs to suppress proliferation and IFN-gamma production by CD4(+)CD25(-) and CD8(+) T cells in patients and controls. Moreover, in both, direct contact of Tregs with their targets leads to increased secretion of regulatory cytokines IL-4, IL-10, and TGF-beta, suggesting a mechanism of linked immunosuppression. Tregs/CD4(+)CD25(-) T cell cocultures lead to similar changes in IFN-gamma and IL-10 secretion in patients and controls, whereas increased TGF-beta secretion is significantly lower in patients. In contrast, in patients, Tregs/CD8(+) T cell cocultures lead to a higher increase of IL-4 secretion. In AIH, Treg FOXP3 expression is lower than in normal subjects. Both in patients and controls, FOXP3 expression is present also in CD4(+)CD25(-) T cells, although at a low level and not associated to suppressive function. Both in patients and controls, addition of Tregs does not influence target cell apoptosis, but in AIH, spontaneous apoptosis of CD4(+)CD25(-) T cells is reduced. In conclusion, Tregs act through a direct contact with their targets by modifying the cytokine profile and not inducing apoptosis. Deficient CD4(+)CD25(-) T cell spontaneous apoptosis may contribute to the development of autoimmunity.

Polyclonal T-cell responses to cytochrome P450IID6 are associated with disease activity in autoimmune hepatitis type 2.

BACKGROUND & AIMS: Autoimmune hepatitis type 2 (AIH-2), a severe juvenile liver disorder of unknown etiology and pathogenesis, is characterized by liver-kidney microsomal antibody type 1 targeting cytochrome P450IID6 (CYP2D6) and is associated to HLA DRB1*07. Although CYP2D6 B-cell reactivity has been extensively characterized, little is known about CYP2D6-specific T-cell responses. The aim of the present study was to characterize anti-CYP2D6 cellular immune responses and their possible pathogenic role in patients with AIH-2. METHODS: We investigated T-cell reactivity against 61 overlapping peptides spanning the full CYP2D6 protein using ex vivo cultures obtained at diagnosis, remission, and relapse. Moreover, CYP2D6-specific T-cell reactivity was investigated in the context of HLA restriction, peptide-binding affinity to HLA DRB1*07, cytokine profile, disease specificity, and clinical course. RESULTS: Proliferative responses to CYP2D6 cluster to 7 antigenic regions in DRB1*07 and to 4 regions in non-DRB1*07 patients. Whereas distinct peptides induce production of interferon gamma, interleukin-4, or interleukin-10, peptides inducing interferon-gamma and proliferation overlap. There is also an overlap between sequences inducing T- and B-cell responses. The breadth (number of epitopes) and intensity (quantity of cytokine produced) of the T-cell response are directly correlated to disease activity (biochemical and histologic markers). CONCLUSIONS: These data imply that the T-cell response to CYP2D6 in AIH-2 is polyclonal, involves multiple effector types targeting different epitopes, and is associated with hepatocyte damage, knowledge that should form the basis for a more refined therapeutic approach.

Neonatal liver disease associated with placental transfer of anti-mitochondrial antibodies.

BACKGROUND: Anti-mitochondrial antibody is the diagnostic hallmark of primary biliary cirrhosis. Its role in the aetiology of primary biliary cirrhosis is controversial. METHODS: Two cases of neonatal hepatitis seropositive for anti-mitochondrial antibody are described. Anti-mitochondrial antibody Ig isotype and epitopic specificity were investigated by immunofluorescence and enzyme immunoassays. RESULTS: In both infants anti-mitochondrial antibody was of the G class, mainly G1 and G3 subclasses, and reacted with two synthetic peptides reproducing major M2 epitopicregions: innerlipoyl domain pyruvate dehydrogenase complex (PDC)-E2(162-176) and PDC-E3 binding protein (PDC-E3BP)86-100. One infant also reacted with outer lipoyl domain PDC-E2(35-49), and 2-oxoglutarate dehydrogenase complex (OGDC)-E2(99-113). An identical pattern of reactivity was present in their mothers, indicating the maternal origin of the antibodies. Anti-mitochondrial antibody disappeared in the infants with the disappearance of the liver pathology. CONCLUSIONS: The simultaneous disappearance of hepatitis and anti-mitochondrial antibody in the infants suggests a possible causal link between the two.