猪SLAⅡ类基因多态性及其与抗病性状关联的研究进展

猪的白细胞抗原(swine lymphocyte antigen,SLA)是猪体内与抗病性和免疫应答密切相关的一组基因群,它不仅编码移植抗原,控制移植排斥反应,还参与免疫应答调控和免疫识别,其中最重要的功能之一就是抗原递呈。对SLA的深入研究不仅可以为兽医临床免疫耐受、表位疫苗的研制提供先进的理论基础,同时还有助于发现猪抗病育种中有效的候选基因。作者就SLAⅡ类基因的多态性及其与抗病性状关联的研究作一综述。

Antiviral innate immunity pathways

Recent studies have uncovered two signaling pathways that activate the host innate immunity against viral infection. One of the pathways utilizes members of the Toll-like receptor （TLR） family to detect viruses that enter the endosome through endocytosis. The TLR pathway induces interferon production through several signaling proteins that ultimately lead to the activation of the transcription factors NF-kB, IRF3 and IRFT. The other antiviral pathway uses the RNA helicase RIG-Ⅰ as the receptor for intracellular viral double-stranded RNA. RIG-Ⅰ activates NF-kB and IRFs through the recently identified adaptor protein MAVS, a CARD domain containing protein that resides in the mitochondrial membrane. MAVS is essential for antiviral innate immunity, but it also serves as a target of Hepatitis C virus （HCV）, which employs a viral protease to cleave MAVS off the mitochondria, thereby allowing HCV to escape the host immune system.

Historical reflections on autoimmune hepatitis

Autoimmune hepatitis(AIH),initially known as chronic active or active chronic hepatitis(and by various other names),first came under clinical notice in the late 1940s.However,quite likely,chronic active hepatitis(CAH) had been observed prior to this and was attributed to a persistently destructive virus infection of the liver.An earlier(and controversial) designation in 1956 as lupoid hepatitis was derived from associated L.E.cell test positivity and emphasized accompanying multisystem features and immunological aberrations.Young women featured prominently in early descriptions of CAH.AIH was first applied in 1965 as a descriptive term.Disease-characteristic autoantibodies were defined from the early 1960s,notably antinuclear antibody(ANA),smooth muscle antibody(SMA) and liver-kidney microsomal(LKM) antibody.These are still widely used diagnostically but their relationship to pathogenesis is still not evident.A liver and disease specific autoantigen has long been searched for but unsuccessfully.Prolonged immunosuppressive therapy with predisolone and azathioprine in the 1960s proved beneficial and remains standard therapy today.AIH like many other autoimmune diseases is associated with particular HLA alleles especially with the "ancestral" B8,DR3 haplotype,and also with DR4.Looking forwards,AIH is one of the several enigmatic autoimmune diseases that,despite being(relatively) organ specific,are marked by autoimmune reactivities with non-organ-specific autoantigens.New paradigms are needed to explain the occurrence,expressions and pathogenesis of such diseases.

Adenoviral-mediated localized CTLA-4Ig gene expression induces long-term allograft pancreas survival and donor-specific immune tolerance in rats

T cell activation following alloantigen recognition plays a critical role in the development of the rejection in all solid organ, tissue and cell transplantation. A recombinant molecule, cytotoxic T lymphocyte antigen 4 antibody （CTLA-4Ig）, is known to induce to T-cell into ＂anergy＂ by blocking the costimulatory B7-CD28 interaction. Either systemic or localized administration of CTLA-Ig has been shown to prolong allograft survival and induce donor-specific tolerance in some transplant models. In this study, we characterized the expression and immunosuppressive effectiveness of adenoviral-mediated CTLA-4Ig gene transfer. We demonstrated transduction of the allografts with AdCTLA-4Ig resulted in localized expression, permanent graft survival and stable donor-specific tolerance. In addition, by performing simultaneous dual-organ through a local expression of CTLA-4Ig via adenoviral-mediated transplantation, we targeted on immunosuppression gene transfer into pancreatic allografts.

Expression of Major Antigen Domains of E2 Gene of CSFV and Analysis of its Immunological Activity

E2 is an envelope glycoprotein of Classical swine fever virus (CSFV) and contains sequential neutralizing epitopes to induce virus-neutralizing antibodies and mount protective immunity in the natural host. In this study, four antigen domains (ABCD) of the E2 gene was cloned from CSFV Shimen strain into the retroviral vector pBABE puro and expressed in eukaryotic cell (PK15) by an retroviral gene expression system, and the activity of recombinant E2 protein to induce immune responses was evaluated in rabbits. The results indicated that recombinant E2 protein can be recognized by fluorescence antibodies of CSFV and CSFV positive serum (Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China) using Western blot, indirect immunofluorescence antibody test (IFAT) and ELISA, Furthermore, anti-CSFV specific antibodies and lymphocyte proliferation were elicited and increased by recombinant protein after vaccination. In the challenge test, all of rabbits vaccinated with recombinant protein and Chinese vaccine strain (C-strain) were fully protected from a rabbit spleen virus challenge. These results indicated that a retroviral-based epitope-vaccine carrying the major antigen domains of E2 is able to induce high level of epitope-specific antibodies and exhibits similar protective capability with that induced by the C-strain, and encourages further work towards the development of a vaccine against CSFV infection.

B cell depletion in treating primary biliary cirrhosis:Pros and cons

Primary biliary cirrhosis (PBC) is a progressive autoim- mune liver disease of unknown etiology that affects almost exclusively women.Ursodeoxycholic acid (UDCA) is currently the only approved drug by Food and Drug Administration for patients with PBC.Although the precise pathogenesis of PBC remains unclear,it has been postulated that many cell populations,including B cells,are involved in the ongoing inflammatory process,which implicates,not surprisingly,a potential thera- peutic target of depleting B cell to treat this disorder.Rituximab is a chimeric anti-CD20 monoclonal antibody that has been approved for the treatment of lymphoma and some autoimmune diseases such as rheumatoid arthritis.Whether it is effective in the treatment of PBC has not been evaluated.Recently,Tsuda et al [1] demon- strated that B cell depletion with rituximab significantly reduced the number of anti-mitochondrial antibodies (AMA)-producing B cells,AMA titers,the plasma levels of immunoglobulins (IgA,IgM and IgG) as well as se- rum alkaline phosphatase,and it was well tolerated by all the treated patients with no serious adverse events.This observation provides a novel treatment option for the patients with PBC who have incomplete response to UDCA.

Celiac disease and microscopic colitis:A report of 4 cases

Celiac disease (CD) is an autoimmune disorder of the small intestine that occurs in genetically predisposed people at all ages.However,it can be associated also to other immunopathological disorders,and may be associated with abnormal histology in segments of the gut other than the small bowel including colonic inflammation.While guidelines for endoscopic investigation of the jejunum are well defined,no indication is defined for colonic investigation.We describe four cases of concurrent CD and microscopic colitis (MC) diagnosed at our department over a 10-year period and analyzed the main features and outcomes of CD in this setting.The symptoms of these patients were improved initially by a gluten-free diet before the onset of MC symptoms.Two of the patients were siblings and had an atypical form of CD.The other two patients with CD and MC also presented with fibrosing alveolitis and were anti-Saccharomyces cerevisiae antibody positive.The co-existence of immune-mediated small bowel and colonic inflammatory and pulmonary diseases are not well-known,and no systematic approach has been used to identify the lifelong patterns of these immune-based diseases.Patients can develop,or present with CD at any stage in life,which can co-exist with other gastrointestinal diseases of (auto-) immune origin.In addition,the fa-milial co-existence and prevalence of MC in patients with a prior diagnosis of CD are unclear.Clinicians managing celiac disease should be aware of these associations and understand when to consider colon investigation.

Autoantibody profiles in autoimmune hepatitis and chronic hepatitis C identifies similarities in patients with severe disease

To determine how the auto-antibodies (Abs) profiles overlap in chronic hepatitis C infection (CHC) and autoimmune hepatitis (AIH) and correlate to liver disease.METHODSLevels of antinuclear Ab, smooth muscle antibody (SMA) and liver/kidney microsomal-1 (LKM-1) Ab and markers of liver damage were determined in the sera of 50 patients with CHC infection, 20 AIH patients and 20 healthy controls using enzyme linked immunosorbent assay and other immune assays.RESULTSWe found that AIH patients had more severe liver disease as determined by elevation of total IgG, alkaline phosphatase, total serum bilirubin and serum transaminases and significantly higher prevalence of the three non-organ-specific autoantibodies (auto-Abs) than CHC patients. Antinuclear Ab, SMA and LKM-1 Ab were also present in 36% of CHC patients and related to disease severity. CHC cases positive for auto-Abs were directly comparable to AIH in respect of most markers of liver damage and total IgG. These cases had longer disease duration compared with auto-Ab negative cases, but there was no difference in gender, age or viral load. KLM-1+ Ab CHC cases showed best overlap with AIH.CONCLUSIONAuto-Ab levels in CHC may be important markers of disease severity and positive cases have a disease similar to AIH. Auto-Abs might have a pathogenic role as indicated by elevated markers of liver damage. Future studies will unravel any novel associations between these two diseases, whether genetic or other.

PRESENCE OF ANTILAMIN ANTIBODIES IN SERA OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

In this study, we characterized specifically-stained sera from patients with systemic lupus erythematosus (SLE) which had been shown to display the homogeneous or peripheral region of nuclei by indirect immunofluorescence (IIF). By western blotting, we demonstrated that in some cases there was a correlation between the peripheral or homogenous. IIF staining of nuclei by sera from patients with SLE and the presence of autoantibodies to lamins. Here we first report the presence of 2. 2% anti-lamin autoantibodies in the sera among the 174 patients with SLE in China.

Human Monoclonal Antibodies as Candidate Therapeutics Against Emerging Viruses and HIV-1

More than 40 monoclonal antibodies (mAbs) have been approved for a number of disease indications with only one of these (Synagis) - for a viral disease, and not for therapy but for prevention. However, in the last decade novel potent mAbs have been discovered and characterized with potential as therapeutics against viruses of major importance for public health and biosecurity including Hendra virus (HeV), Nipah virus (NiV), severe acute respiratory syndrome coronavirus (SARS-CoV), Ebola virus (EBOV), West Nile virus (WNV), influenza virus (IFV) and human immunodeficiency virus type 1 (HIV-1). Here, we review such mAbs with an emphasis on antibodies of human origin, and highlight recent results as well as technologies and mechanisms related to their potential as therapeutics.

Microscopic colitis

Microscopic colitis may be defined as a clinical syndrome, of unknown etiology, consisting of chronic watery diarrhea, with no alterations in the large bowel at the endoscopic and radiologic evaluation. Therefore, a definitive diagnosis is only possible by histological analysis. The epidemiological impact of this disease has become increasingly clear in the last years, with most data coming from Western countries. Microscopic colitis includes two histological subtypes [collagenous colitis (CC) and lymphocytic colitis (LC)] with no differences in clinical presentation and management. Collagenous colitis is characterized by a thickening of the subepithelial collagen layer that is absent in LC. The main feature of LC is an increase of the density of intra-epithelial lymphocytes in the surface epithelium. A number of pathogenetic theories have been proposed over the years, involving the role of luminal agents, autoimmunity, eosinophils, genetics (human leukocyte antigen), biliary acids, infections, alterations of pericryptal fibroblasts, and drug intake; drugs like ticlopidine, carbamazepine or ranitidine are especially associated with the development of LC, while CC is more frequently linked to cimetidine, non-steroidal antiinflammatory drugs and lansoprazole. Microscopic colitis typically presents as chronic or intermittent watery diarrhea, that may be accompanied by symptoms such as abdominal pain, weight loss and incontinence. Recent evidence has added new pharmacological options for the treatment of microscopic colitis:the role of steroidal therapy, especially oral budesonide, has gained relevance, as well as immunosuppressive agents such as azathioprine and 6-mercaptopurine. The use of anti-tumor necrosis factoragents, infliximab and adalimumab, constitutes a new, interesting tool for the treatment of microscopic colitis, but larger, adequately designed studies are needed to confirm existing data.

ANALYSIS OF THE ANTIGEN-ANTIBODY SPECIFICITY IN THE SEMEN OF PATIENTS WITH NEISSERIA GONORRHOEAE

This study was done to define the human genital immune response to infection with Neisseria gonorrhoeae. The semen specimens were obtained from 15 patients with uncomplicated gonococcal infection in the acute and convalescent phases and 15 men with uninfected control- After precipitated with amoniasulfate,the semen was tested against the outer membrane protein of gonococcal isolates from the same patients to examine antigen-antibody interactions by use of the western blot technique. The antibodies in the semen reacted with more gonococcal antigens in the acute phase than in the convalescent phase. IgA in the semen reacted with more antigens than did IgG in the same specimens. The predominant reacted antigens were protein I, protein II, 46～ 48, kD, 14 ～16 kD and 88～ 90 kD protein.

B cells biology in systemic lupus erythematosus—from bench to bedside

Systemic lupus erythematosus(SLE) is a debilitating autoimmune disease that can involve multi-organs. B cells play a central role in the immunopathogenesis via antibody-dependent and antibody-independent ways. Excessive autoantibodies production, hyperresponsiveness and prolonged survival of autoreactive B cells are characteristics of SLE. In this article, mechanisms of self-tolerance loss of B cells and promising B cell-targeting therapies in lupus are reviewed and discussed.