Interleukin-33 (IL-33) is a novel cytokine and belongs to IL-1 family expressed in a wide range of organs and cells. IL-33 is a dual-functional molecule: as a classical cytokine it induces immune response and it also regulates gene transcription in the nucleus. Altered expression of IL-33 has been observed in various human diseases such as inflammation, autoimmune diseases, and virus infection. The article reviews advances on immune function of IL-33 and its relation to a variety of human diseases.
Autoimmune Diseases ; immunology ; Humans ; Inflammation ; immunology ; Interleukin-33 ; Interleukins ; immunology

Autoimmune Diseases ; immunology ; Gene Expression Regulation ; immunology ; Humans ; Immunoglobulin G ; genetics ; immunology ; Sclerosis ; genetics ; immunology ; pathology

Natural killer T cells are innate-like and tissue-resident lymphocytes, which recognize lipid antigens and are enriched in the liver. Natural killer T cells play important roles in infections, tumors, autoimmune diseases, and metabolic diseases. In this study, we summarize recent findings on biology of natural killer T cells and their roles in hepatitis B virus and hepatitis C virus infection, autoimmune liver diseases, alcoholic liver disease, nonalcoholic fatty liver disease, and hepatocellular carcinoma. Controversial results from previous studies are discussed, and indicate the dynamic alteration in the role of natural killer T cells during the progression of liver diseases, which might be caused by changes in natural killer T subsets, factors skewing cytokine responses, and intercellular crosstalk between natural killer T cells and CD1d-expressing cells or bystander cells.
Animals ; Autoimmune Diseases ; immunology ; Humans ; Liver ; pathology ; Liver Diseases ; immunology ; Natural Killer T-Cells ; immunology

Immunoglobulin G4-related systemic disease (IgG4-RSD) is a recently defined emerging entity characterized by a diffuse or mass forming inflammatory reaction rich in IgG4-positive plasma cells associated with fibrosclerosis and obliterative phlebitis. IgG4-RSD usually affects middle aged and elderly patients, with a male predominance. It is associated with an elevated serum titer of IgG4, which acts as a marker for this recently characterized entity. The prototype is IgG4-related sclerosing pancreatitis or autoimmune pancreatitis (AIP). Other common sites of involvement are the hepatobiliary tract, salivary gland, orbit, and lymph node, however practically any organ can be involved, including upper aerodigestive tract, lung, aorta, mediastinum, retroperitoneum, soft tissue, skin, central nervous system, breast, kidney, and prostate. Fever or constitutional symptoms usually do not comprise part of the clinical picture. Laboratory findings detected include raised serum globulin, IgG and IgG4. An association with autoantibody detection (such as antinuclear antibodies and rheumatoid factor) is seen in some cases. Steroid therapy comprises the mainstay of treatment. Disease progression with involvement of multiple organ-sites may be encountered in a subset of cases and may follow a relapsing-remitting course. The principal histopathologic findings in several extranodal sites include lymphoplasmacytic infiltration, lymphoid follicle formation, sclerosis and obliterative phlebitis, along with atrophy and destruction of tissues. Immunohistochemical staining shows increased IgG4+ cells in the involved tissues (>50 per high-power field, with IgG4/IgG ratio >40%). IgG4-RSD may potentially be rarely associated with the development of lymphoma and carcinoma. However, the nature and pathogenesis of IgG4-RSD are yet to be fully elucidated and provide immense scope for further studies.
Autoimmune Diseases/*immunology ; Cholangitis, Sclerosing/*immunology ; Humans ; Immunoglobulin G/*immunology ; Lacrimal Apparatus/immunology ; Lymphatic Diseases/*immunology ; Pancreatitis, Chronic/*immunology ; Salivary Glands/immunology ; Sclerosis/immunology

Immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disease. It is considered that production of platelet auto-antibodies was one of the pathogenesis of ITP, first-line therapy including corticosteroid and immunoglobulin could reduce destruction of platelets by inhibiting production of auto-antibodies and blocking Fc-receptor of reticuloendothelial system, but some of the patients were refractory to first-line therapy and have persistent duration of the disease, having worse prognosis and developing into chronic/refractory ITP(C/RITP) . Platelet membrane glycoprotein like GPIIb/IIIa and GPIbα are the most common antigen targets, but first-line therapy was less effective to patients whose anti-GPIbα antibodies are positive. Further studies revealed that the way causing platelet destruction by anti-GPIIb/IIIa antibodies and anti-GPIbα antibodies are different: the former is mainly dependent to Fc-pathway, and the latter mainly cleared platelet by Fc-independent way. Results above indicated that detection of type of platelet auto-antibodies maybe potential to treatment and prognosis of ITP. This article summarizes relationship between platelet specific antibodies and the onset, clinical manifestation, treatment and prognosis of ITP.
Antibodies ; immunology ; Autoimmune Diseases ; Blood Platelets ; immunology ; Humans ; Platelet Membrane Glycoproteins ; Prognosis ; Thrombocytopenia ; immunology ; therapy

Animals ; Autoimmune Diseases ; etiology ; immunology ; Dendritic Cells ; immunology ; Humans ; Lupus Erythematosus, Systemic ; etiology ; immunology

OBJECTIVETo investigate the main components of inner ear antigens inducing autoimmune Meniere's disease (AIMD) in guinea pigs.

METHODSThe guinea pigs were immunized with isologous crude inner ear antigens (ICIEAg). Then, the hearing function was measured with auditory brainstem response (ABR), the vestibular function was measured with electronystagmography (including spontaneous nystagmus and caloric test), and inner ear histopathological changes were observed by inner ear celloidin section with haematoxylin-eosin staining and observed under light microscope. According to these results, the AIMD-model animals from non-AIMD-model ones were distinguished. The special antibodies against ICIEAg in sera were measured with ELISA. The antigen-antibody reactions against different components of ICIEAg were detected by Western blotting with sera of AIMD and non-AIMD guinea pigs respectively. Then, we analysed the contrast between them and found the main components of the ICIEAg that were positive reaction in AIMD guinea pigs and negative reaction in non-AIMD guinea pigs.

RESULTSThe result of ELISA demonstrated that the sera of both the AIMD and non-AIMD guniea pigs contained the special antibodies against ICIEAg after immunized with ICIEAg. The difference of the amount of antibody against ICIEAg between AIMD guinea pig group and non-AIMD guinea pig group was not significant. Western blotting assay showed only the sera of AIMD guinea pig contained the antibodies against the specific antigens with the molecular of 68 000, 58 000, 42 000 and 28 000.

CONCLUSIONSICIEAg contain many different components, the AIMD might only happen in the guinea pigs in which the special immunization against the main components that could induce this kind of disorder appeared. The inner ear antigens with molecular of 68 000, 58 000, 42 000 and 28 000 might be the main components inducing AIMD in guinea pigs.

Animals ; Autoantigens ; immunology ; Autoimmune Diseases ; immunology ; Disease Models, Animal ; Ear, Inner ; immunology ; Guinea Pigs ; Labyrinth Diseases ; immunology

OBJECTIVETo identify the candidate auto-antigen of rheumatic heart disease as a molecular marker for this disease.

METHODSThe total RNA of the heart tissue of patients with rheumatic heart disease was extracted and reverse-transcribed into long cDNA to construct the phage expression library. The library was screened using the serum from patients with active rheumatic fever, and the positive clone was identified and analyzed by bioinformatics and expressed in vitro. The expressed products were evaluated with Western blotting and its cross-reactivity was assessed.

RESULTSThe phage expression library of the heart tissue of patients with rheumatic heart disease was constructed, with the titer of the primary library of 3.3×10(6) pfu/ml, recombinant rate of 99%, and 81% of the inserted segments were larger than 1 kb. An auto-antigen RHDAG1 was identified by screening, which was homologous to keratin 18. RHDAG1 was detected in the serum of patients with active rheumatic fever and of those with rheumatic heart disease, but not in the serum of healthy subjects.

CONCLUSIONPhage display library can be an effective strategy to screen the auto-antigens of rheumatic heart disease. The auto-antigen RHDAG1 can be a candidate molecular biomarker of rheumatic heart disease and/or rheumatic fever.

Autoantibodies ; blood ; immunology ; Autoantigens ; immunology ; isolation & purification ; Autoimmune Diseases ; blood ; immunology ; Humans ; Peptide Library ; Rheumatic Heart Disease ; immunology

Objective To explore the clinical characteristics of autoimmune disease with dual seropositive antibodies of leucine-rich glioma inactivated 1(LGI1)and contactin-associated protein 2(Caspr2).Methods The clinical data of seven patients with dual seropositive LGI1 and Caspr2 antibodies who were admitted to the Neurology Department of Peking Union Medical College Hospital from July 2014 to December 2017 were retrospectively analyzed.Results Central,peripheral and autonomic nervous systems were all involved in the seven cases;100%(7/7)presented with insomnia,myokymia,neuropahic pain and hyperhydrosis;71%(5/7)showed memory decline or psychiatric and behavioral symptoms;57%(4/7)had urinary hesitation or constipation;and 43%(3/7)had seizure.Electromyography showed 100%(6/6) of the patients had prolonged afterdischarges following normal M waves and/or abnormal spontaneous firing.Electroencephalography revealed slow waves or basic rhythm slowing in 71%(5/7)of patients.Electrocardiography showed sinus tachycardia,axis deviation,and prolonged QT intervals in 71%(5/7)of patients.One patient died from arrhythmia before immunotherapy.One died from pulmonary infection after immunotherapy.Improvement with immunotherapy was documented in the other five cases.No relapse was noted during the 1-2-year follow-up.Conclusions Autoimmune disease with dual seropositive antibodies of LGI1 and Caspr2 can diffusely affect the central,peripheral,and autonomic nervous systems.The possibility of this disease should be considered in patients with acute and subacute onset of neuropsychiatric symptoms,especially in patients with accompanying insomnia,myokymia,and hyperhydrosis.
Autoantibodies ; blood ; Autoimmune Diseases ; immunology ; Humans ; Membrane Proteins ; immunology ; Nerve Tissue Proteins ; immunology ; Proteins ; immunology ; Retrospective Studies

OBJECTIVE: To purify P0 protein from guinea pig's inner ear by preparative SDS-PAGE and to study the possible role it may play in the etiology of autoimmune inner ear disease. METHOD: A mixture of membraneous proteins of inner ear was separated by preparative SDS-PAGE. The corresponding band at 30,000 was cut and electrically eluted. The protein collected was identified by analytical SDS-PAGE and Western blot assay. A group of 20 guinea pigs were immunized with P0 protein emulsified in complete Freunds adjuvant, another 10 guinea pigs were immunized with complete Freunds adjuvant only as control. The guinea pigs' hearing thresholds, serum IgG level and morphological changes in the inner ear were investigated. The distribution of P0 protein in the cochlear was detected by immunohistochemical technique. RESULT: The purity of the protein was demonstrated by a single band at the 30000 site in SDS-PAGE, which was identified as P0 protein by western blot analysis assay. About 17.5% P0-immunized guinea pigs showed increased hearing thresholds, elevated IgG level (F = 6.48, P<0.01), as well as a decreased number of spiral ganglion cells and inflammatory cell infiltration in the cochlear nerve region. The P0 protein is distributed in the cochlear nerve and spiral ganglion only. CONCLUSION P0 protein from guinea pigs in ner ear can be successfully purified by preparative SDS-PAGE and an animal model of experimental autoimmune inner ear disease induced by P0 protein was successfully established.
Animals ; Autoimmune Diseases ; immunology ; Disease Models, Animal ; Guinea Pigs ; Labyrinth Diseases ; immunology ; Myelin P0 Protein ; immunology ; isolation & purification