Virological profiles in hepatitis B virus inactive carriers: monthly evaluation in 1-year follow-up study.

STUDY SUBJECT: We longitudinally evaluated the virological behaviour and the hepatitis B virus (HBV) genomic variability in inactive HBV surface antigen (HBsAg) chronic carriers. PATIENTS AND METHODS: Fourteen HBsAg-positive healthy workers (13 inactive carriers and 1 with active HBV infection) were followed up for 12 months by monthly evaluation of aminotransferase, HBV DNA, and IgM anti HBV core antigen (IgM anti-HBc) values. Moreover, HBV serum isolates from each case were amplified, cloned and sequenced to evaluate the presence of the potentially clinical relevant core-promoter and precore mutations. The same technical procedures were used to examine the S gene of isolates from 3 randomly selected inactive carriers and the patients with active HBV infections. RESULTS: Aminotransferase values were constantly normal in all cases. Viremia levels appear to fluctuate widely over time in each individual case, although the HBV DNA remained below 2 x 10(4) copies/ml in all samples. Only four serum samples from two inactive carriers had IgM anti-HBc values higher than the specific cut-off limit of the assay. Either wild type or core-promoter/precore HBV variants or a mixture of them were detected in the inactive carriers. S gene nucleotide homology among the clones from the three inactive carriers and the subject with active infection was 98.9%, 98.3%, 98.1% and 98.2%, respectively. CONCLUSIONS: The degree of suppression of HBV replication in inactive carriers is variable over time, and the entity and quality of HBV variability is comparable between active and inactive carriers.     

Mumps disease outbreak in Davangere district of Karnataka,India

Background: Mumps is a vaccine-preventable disease that usually occurs as a parotitis, but it can also lead to several life- threatening complications, including pancreatitis, meningitis and encephalitis. Objective: To determine and diagnosis of mumps disease, which is communicable disease usually affects childrens. Although it is seen worldwide, but outbreaks not common in India. Materials and Methods: Thirty one suspected mumps cases, who presented to the unimmunized population of Chikkahallivana village in Davangere district of Karnataka, India in January 2014, with clinical evidence of fever, cervical lymphadenitis and ear pain, manifest with self-limited uni-or bilateral parotitis. A total of 31 cases consisting of 31 blood and 31 throat swabs were tested for diagnosis of mumps disease. Results: Of the 31 suspected cases, laboratory results showed 18 positive for mumps IgM antibodies and 7 cases showed presence of mumps virus RNA by RT-PCR using MV specific nested primers. From 31 cases, 5 were positive with both the methods. Conclusion: We confirmed the cases by serological as well as a sensitive RT-nested PCR-based method and sequencing results for the molecular identification of mumps infection. Sequencing results of the SH gene identified outbreak strain as genotype C, which was consistent with other outbreaks in India.     

Anti-HBc of IgM-class,HBeAg and anti-HBe in acute and chronic hepatitis B

ABSTRACT— The presence and persistence of IgM antibody against hepatitis B core antigen (anti-HBc IgM) and the correlation with other HBV markers were studied in 42 patients, all of whom had acute HBsAg-positive hepatitis but whose subsequent diseases differed. All patients initially had anti-HBc IgM. In 13 out of 15 patients with uncomplicated acute hepatitis, anti-HBc IgM disappeared within 6 months after onset of the disease. In five out of 12 patients, who in spite of transient HBsAg developed chronic liver disease, the anti-HBc IgM persisted for more than 2 years. Among 15 patients with persistent HBsAg, anti-HBc IgM was present from 7 months to more than 8 years. Seroconversion from HBeAg to anti-HBe was observed in seven patients and in five of these anti-HBc IgM disappeared during the follow-up period. These results indicate that anti-HBc IgM can be used as a serological marker of recent or ongoing HBV infection.     

Interferon treatment in hepatitis B surface antigen-positive hepatitis B e antibody-positive chronic hepatitis B: role of hepatitis B core antibody IgM titre in patient selection and treatment monitoring

Chronic hepatitis B infection with the hepatitis B e antigen (HBeAg)-negative variant is associated with a severe clinical course and a low response rate to interferon (IFN). In an attempt to improve the chances of sustained response to interferon we designed a pilot study, using titres of IgM antibodies to hepatitis B core antigen (HBcAb IgM) to guide treatment initiation. Eighteen adults who were HBeAg-negative with biopsy-proven chronic active hepatitis (seven with cirrhosis) entered the study. They were followed-up bimonthly with routine liver function tests, and HBcAb IgM titres were also determined. Treatment (lymphoblastoid IFN 5 million units (MU) m^–2 three times weekly for 6 months) was started when the HBcAb IgM titre was increasing. Fifteen (83.3%) patients had normal alanine aminotransferase (ALT) levels and undetectable HBV DNA at the end of treatment. HBcAb IgM decreased in all responders. We observed a relapse in four patients (three with cirrhosis), in the first year after treatment, with an increase in ALT, HBV DNA and titre of HBcAb IgM. Eleven patients (61.1%) had a sustained response and eight of these 11 patients were followed-up for more than 18 months; two responders cleared hepatitis B surface antigen (HBsAg). Hence, the rate of sustained response to IFN in HBeAb-positive patients with chronic hepatitis is improved if treatment is started when HBcAb IgM levels are increasing.     

Clonal B-cell expansions in peripheral blood of HCV-infected patients

Summary. Clonal expansions of IgM-producing B cells were investigated in 38 patients with a chronic hepatitis C virus infection. Eight patients were affected with type II mixed cryoglobulinaemia (two of whom also had non-Hodgkin's lymphoma and one had Waldenstrom's disease), one with type III mixed cryoglobulinaemia, one with Waldenstrom's disease, and 28 with chronic liver disease. To detect the clonal B-cell expansions we used a RT/PCR procedure in which the CDR3/FW4 regions of the IgM heavy chain mRNAs were amplified and resolved in sequencing poly-acrylamide gels. Clonal Ig gene rearrangements were detected in all patients with type II mixed cryoglobulinaemia and also at a high frequency (24%) in the HCV-infected patients without cryoglobulinaemia. A polyclonal pattern was present in the patient with type III mixed cryoglobulinaemia and in the 15 normal individuals and 16 age-related patients with HCV-negative alcoholic liver disease which were investigated as controls. No association was found between the presence of a clonal B-cell expansion and age, sex, liver histology, or levels of serum aminotransferase. The serum levels of rheumatoid factor were increased in all patients with a clonal expansion, suggesting that the expanded B-cell clones belong to the rheumatoid factor producing B-cell subset.     

Pathogenicity of IgA and/or IgM antibodies to heparin–PF4 complexes in patients with heparin-induced thrombocytopenia

Antibodies to heparin–PF4 (H-PF4) complexes have been tested and isotyped in 38 patients who developed severe heparin-induced thrombocytopenia (type II HIT). All the patients had a platelet count < 120 × 10⁹/l or a reduction of >30% of the initial value, occurring at least 5 d after the onset of heparin. Thrombocytopenia, which rapidly reversed following the withdrawal of heparin, was associated with thrombosis in nine patients. Although IgG isotypes were found in most cases ( n  = 26), the presence of only IgM and/or IgA was observed in 12 patients, including three cases showing a thrombotic complication. Our results indicate that type II HIT may be induced by IgA and/or IgM anti-H-PF4 antibodies even in the absence of IgG isotypes. This finding demonstrates that platelet Fc receptors (FcγRII) are not necessarily involved in the pathogenicity of heparin-dependent antibodies and emphasizes the major role of platelet PF4 receptors. The increased expression of the latter following a slight activation by thrombin, and the subsequent binding of IgM and IgA antibodies to H-PF4 on the platelet surface, may directly trigger platelet activation, aggregation and thrombosis. Alternatively, thrombocytopenia could be indirectly induced through the mediation of neutrophils, monocytes and lymphocytes which expose receptors for IgA (FcαR) or IgM (FcμR). IgM–platelet complexes may also bind and activate complement, leading to platelet activation or destruction. Moreover, the reactivity of the antibodies with glycosaminoglycans–PF4 complexes present on the endothelial surface could also induce endothelial lesions and promote procoagulant activity and predisposition to thrombosis.     

Coxsackie B virus IgM in children at onset of Type 1 (insulin-dependent) diabetes mellitus: evidence for IgM induction by a recent or current infection

Summary Thirty-five children with newly-diagnosed Type 1 (insulin-dependent) diabetes mellitus and their 47 siblings were investigated for the presence of IgM antibodies to Coxsackie B virus serotypes 1–5 (CBV1-5) with the aid of -antibody-capture radioimmunoassays. When a high cut-off value was used, 16 (46%) diabetic children and 16 (34%) siblings showed CBV-IgM. Of the siblings of diabetic patients positive for CBV-IgM, 11 (44%) were CBV-IgM-positive; the corresponding figure for the siblings of negative patients was five (26%). With a lower cut-off value, leading to a borderline titre, the frequency of IgM positivity increased in both the patients and siblings. When the borderline titres were included, the number of IgM-positive patients was 19 (54%) and the corresponding number of siblings was 29 (62%). Of the siblings of positive patients, 27 (93 %) showed CBV-IgM, and of the siblings of the negative patients, two (11 %) were CBV-IgM-positive. Sixteen (89 %) siblings of IgM-negative patients remained negative. Regarding the serotypes of CB V to which IgM was directed, CBV 4 was most frequent, followed by serotypes CBV 3, CBV 2, CBV 5 and CBV 1. There was a striking similarity between the individual diabetic child and his or her sibling(s) concerning this specificity of IgM. It is concluded that within most families with a newly-diagnosed diabetic child positive for CBV-IgM the same serotype(s) of the virus circulates and that the intrafamilial spread of virus is considerable. The results strongly indicate that the IgM detected was CBV-specific and caused by a recent or current CBV infection. It is highly probable that the same strain of virus was present in different members of the same family. Therefore, if diabetogenic CBV strains do in fact exist, additional factors must be of importance for the development of Type 1 diabetes in children infected with such a CBV strain but remaining non-diabetic.     

ELISA对幽门螺杆菌感染血清IgG,IgA,IgM抗体检测的诊断价值

应用酶联免疫吸附试验（ＥＬＩＳＡ）对无选择性作内镜检查的９０例患者血清，分别作抗ＨＰＩｇＧ，ＩｇＡ，ＩｇＭ特异性抗体的检测，同时与胃粘膜活检组织块的镜检，培养，快速尿素酶试验的结果进行比较。ＥＬＩＳＡ检测结果显示血清ＩｇＧ，ＩｇＡ，ＩｇＭ抗体的阳性率分虽为７１．１％（６４／９０），５６．６％（５１／９０），５６．６％（５１／９０），ＩｇＧ检出率均高于检法６５．６％％（５９／９０），尿素酶试验５５．     

先天性感染日本血吸虫家兔攻击感染后血清抗体动态的进一步研究

目的运用日本血吸虫成虫抗原和虫卵抗原检测日本血吸虫先天性感染仔兔攻击感染后的血清特异性IgG、IgM抗体并观察其动态变化,探讨仔兔先天性感染后的体液免疫应答.方法10只怀孕晚期母兔分为三组:4只孕兔人工感染700条日本血吸虫尾蚴/只,所产仔兔为先天性感染组(G1);3只孕兔人工感染700条日本血吸虫尾蚴/只,所产仔兔于出生后第55天攻击感染20条尾蚴/只,该组仔兔为先天性感染且攻击感染组(G2);3只孕兔不感染,正常分娩的健康同龄仔兔感染20条尾蚴/只作对照C组.三组仔兔分别于出生后第53、67、81、95天采血收集血清,分别运用AWA-ELISA及SEA-ELISA法检测血清特异性IgG、IgM抗体,观察动态变化.结果仔兔先天性感染率为66.7%(10/15);G2组和G1组10只先天性感染仔兔相比较,血清特异性IgG、IgM抗体动态规律均比较接近,无论是AWA-ELISA还是SEA-ELISA检测,出生后第95天仔兔IgG、IgM抗体0D均值在两组间差异均没有显著性(P＞0.05);对照组仔兔血清IgG、IgM出生后第95天检测几乎全部呈阳性,抗体阳性仔兔数明显多于同期G1、G2组,且0D均值也显著高于同期G1、G2组(P＜0.05).结论先天性感染日本血吸虫的仔兔血清抗体呈低免疫反应状态(hypo-responsiveness),可能存在免疫耐受,攻击性感染不能诱导仔兔免疫系统产生明显的保护性免疫.