Aging is a complex process associated with dysregulation of the immune system and low levels of inflammation, often associated with the onset of many pathologies. The lacrimal gland (LG) plays a vital role in the maintenance of ocular physiology and changes related to aging directly affect eye diseases. The dysregulation of the immune system in aging leads to quantitative and qualitative changes in antibodies and cytokines. While there is a gradual decline of the immune system, there is an increase in autoimmunity, with a reciprocal pathway between low levels of inflammation and aging mechanisms. Elderly C57BL/6J mice spontaneously show LGs infiltration that is characterized by Th1 but not Th17 cells. The aging of the LG is related to functional alterations, reduced innervation and decreased secretory activities. Lymphocytic infiltration, destruction, and atrophy of glandular parenchyma, ductal dilatation, and secretion of inflammatory mediators modify the volume and composition of tears. Oxidative stress, the capacity to metabolize and eliminate toxic substances decreased in aging, is also associated with the reduction of LG functionality and the pathogenesis of autoimmune diseases. Although further studies are required for a better understanding of autoimmunity and aging of the LG, we described anatomic and immunology aspects that have been described so far.
Aged ; Aging ; Allergy and Immunology ; Animals ; Antibodies ; Atrophy ; Autoimmune Diseases ; Autoimmunity ; Cytokines ; Dilatation ; Eye Diseases ; Humans ; Immune System ; Inflammation ; Lacrimal Apparatus ; Mice ; Ocular Physiological Phenomena ; Oxidative Stress ; Pathology ; Tears ; Th17 Cells

OBJECTIVEAbnormal maternal thyroid function is associated with preterm birth. However, this association stays dubious in relevant individual studies for ethnic difference reasons and lack of direct supporting data. This study aimed to evaluate the relationship between preterm birth and thyroid dysfunction or autoimmunity based on ethnic differences.

METHODSRelevant studies were identified through searches of MEDLINE, Excerpta Medica, Wan Fang, China Biological Medicine disc, and China National Knowledge Infrastructure from inception to June 15, 2016. Original articles in which an incidence or prevalence of thyroid dysfunction or autoimmunity before second trimester of pregnancy could be extracted were included.

RESULTSThirty-two unique studies were included for the final meta-analysis. Patients involved were divided into two groups: Group 1 (G1) and Group 2 (G2) comprising of Asian and Caucasian populations, respectively. Positive thyroid antibodies were associated with the occurrence of preterm birth in both G1 [odds ratio (OR): 3.62, 95% confidence interval (CI): 2.83-4.65] and G2 (OR: 1.35, 95% CI: 1.17-1.56); hypothyroidism, only in G2 (OR: 1.20, CI: 1.09-1.33); and subclinical hypothyroidism or hypothyroxinemia, in neither group.

CONCLUSIONThyroid autoimmunity may be a more favorable factor leading to preterm birth among pregnant women of different ethnicities, compared with thyroid dysfunction.

Autoimmune Diseases ; ethnology ; immunology ; physiopathology ; Autoimmunity ; Female ; Humans ; Infant, Newborn ; Male ; Pregnancy ; Pregnancy Complications ; ethnology ; immunology ; physiopathology ; Premature Birth ; ethnology ; immunology ; physiopathology ; Thyroid Diseases ; ethnology ; immunology ; physiopathology ; Thyroid Gland ; physiopathology

Human genetic variation is represented by the genetic differences both within and among populations, and most genetic variants do not cause overt diseases but contribute to disease susceptibility and influence drug response. During the last century, various genetic variants, such as copy number variations (CNVs), have been associated with diverse human disorders. Here, we review studies on the associations between CNVs and autoimmune diseases to gain some insight. First, some CNV loci are commonly implicated in various autoimmune diseases, such as Fcgamma receptors in patients with systemic lupus erythemoatosus or idiopathic thrombocytopenic purpura and beta-defensin genes in patients with psoriasis or Crohn's disease. This means that when a CNV locus is associated with a particular autoimmune disease, we should examine its potential associations with other diseases. Second, interpopulation or interethnic differences in the effects of CNVs on phenotypes exist, including disease susceptibility, and evidence suggests that CNVs are important to understand susceptibility to and pathogenesis of autoimmune diseases. However, many findings need to be replicated in independent populations and different ethnic groups. The validity and reliability of detecting CNVs will improve quickly as genotyping technology advances, which will support the required replication.
Animals ; Autoimmune Diseases/ethnology/*genetics/immunology ; Autoimmunity/*genetics ; *DNA Copy Number Variations ; *Gene Dosage ; Genetic Association Studies ; Genetic Markers ; Genetic Predisposition to Disease ; Humans ; Phenotype ; Population Groups/genetics ; Risk Factors

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most prevalent type of encephalitis. Investigating the pathogenesis of anti-NMDAR encephalitis will enhance our understanding of this disease and play a central part in providing reasonable treatment for the patients. The pathogenesis is elucidated as follows: (1) the findings of the relationship between anti-NMDAR encephalitis and tumors; (2) further research on the relationship between anti-NMDAR encephalitis and tumors; (3) NMDAR epitopes and the autoimmunity of patients; (4) the interaction between antibody and NMDAR; (5) the pathogenesis of anti-NMDAR encephalitis without tumors. This review gives a brief introduction to the methodology and way of finding out the valuable clinical problems and making a clear and explicit explanation of them by exhibiting the process of discovering the disease, disclosing its relationship with tumors, and investigating its pathological and molecular mechanism. Current studies have demonstrated that anti-NMDAR encephalitis is an autoimmune disease of the nervous system that is closely associated with tumors, particularly ovarian teratoma.
Anti-N-Methyl-D-Aspartate Receptor Encephalitis ; etiology ; Antibodies ; immunology ; Autoimmunity ; Humans ; Neoplasms ; complications ; Receptors, N-Methyl-D-Aspartate ; immunology

We describe an unusual case of systemic lupus erythematosus with pulmonary manifestations presenting as hypoglycemia due to anti-insulin receptor antibodies. A 38-year-old female suffered an episode of unconsciousness and was admitted to hospital where her blood glucose was found to be 18 mg/dL. During the hypoglycemic episode, her serum insulin level was inappropriately high (2,207.1 pmol/L; normal range, 18 to 173) and C-peptide level was elevated (1.7 nmol/L; normal range, 0.37 to 1.47). Further blood tests revealed the presence of antinuclear antibodies, anti-double-stranded DNA antibodies, and anti-Ro/SSA, anti-La/SSB, anti-ribonucleoprotein, and anti-insulin receptor antibodies. A computed tomography scan of the abdomen, aimed at tumor localization, such as an insulinoma, instead revealed ground-glass opacities in both lower lungs, and no abnormal finding in the abdomen. For a definitive diagnosis of the lung lesion, video-associated thoracoscopic surgery was performed and histopathological findings showed a pattern of fibrotic non-specific interstitial pneumonia.
Adult ; Autoantibodies/*blood ; *Autoimmunity ; Biological Markers/blood ; Blood Glucose/metabolism ; Female ; Humans ; Hypoglycemia/blood/*complications/immunology ; Insulin/blood ; *Insulin Resistance ; Lung Diseases, Interstitial/diagnosis/*etiology/immunology/surgery ; Lupus Erythematosus, Systemic/*complications/diagnosis/immunology ; Receptor, Insulin/*immunology ; Thoracic Surgery, Video-Assisted ; Tomography, X-Ray Computed ; Treatment Outcome

T cell recognition of foreign peptide antigen and tolerance to self peptides is key to the proper function of the immune system. Usually, in the thymus T cells that recognize self MHC + self peptides are deleted and those with the potential to recognize self MHC + foreign peptides are selected to mature. However there are exceptions to these rules. Autoimmunity and allergy are two of the most common immune diseases that can be related to recognition of self. Many genes work together to lead to autoimmunity. Of those, particular MHC alleles are the most strongly associated, reflecting the key importance of MHC presentation of self peptides in autoimmunity. T cells specific for combinations of self MHC and self peptides may escape thymus deletion, and thus be able to drive autoimmunity, for several reasons: the relevant self peptide may be presented at low abundance in the thymus but at high level in particular peripheral tissues; the relevant self peptide may bind to MHC in an unusual register, not present in the thymus but apparent elsewhere; finally the relevant self peptide may be post translationally modified in a tissue specific fashion. In some types of allergy, the peptide + MHC combination may also be fully derived from self. However the combination in question may be modified by the presence of other ligands, such as small drug molecules or metal ions. Thus these types of allergies may act like the post translationally modified peptides involved some types of autoimmunity.
Animals ; Autoantigens ; immunology ; Autoimmunity ; HLA Antigens ; immunology ; Humans ; Hypersensitivity ; immunology ; Receptors, Antigen, T-Cell ; metabolism ; T-Lymphocytes ; immunology ; metabolism

Primary biliary cirrhosis (PBC) is a slowly progressive cholestatic liver disease of autoimmune etiology. The initial presentation of PBC is various from asymptomatic, abnormal liver biochemical tests to overt cirrhosis. The diagnosis of PBC is based on cholestatic biochemical liver tests, presence of antimitochondrial antibody and histologic findings of nonsuppurative destructive cholangitis. Although the diagnosis is straightforward, it could be underdiagnosed because of its asymptomatic presentation, or underrecognition of the disease. UDCA in a dose of 13-15 mg/kg is the widely approved therapy which can improve the prognosis of patients with PBC. However, one-third of patients does not respond to UDCA therapy and may require liver transplantation. Every effort to diagnose PBC in earlier stage and to develop new therapeutic drugs and clinical trials should be made.
Autoantibodies/blood ; Autoimmunity/immunology ; Cholagogues and Choleretics/therapeutic use ; Humans ; Liver Cirrhosis, Biliary/*diagnosis/pathology/*therapy ; Liver Transplantation ; Ursodeoxycholic Acid/therapeutic use

OBJECTIVETo explore the effects of removing dampness and promoting diuresis method on autoimmune and immuno-inflammatory response caused by nucleus pulposus of rats, in order to provide the basis for the treatment of lumbar disc herniation with Chinese medical immunotherapy.

METHODSForty male Wistar rats were divided into 4 groups randomly according to body weight layer:sham operation group (group A), model contrast group (group B), colchicine tablets group (group C), modified Qingyao decoction group (group D). There were 10 rats in each group. Nucleus pulposus of coccygeal vertebra was transplanted to the gluteal muscle by operation in groups B, C, D, which can lead to autoimmune and immuno-inflammatory response of rats; the rats of group A were only treated with sham operation. At the 3rd day after operation, the rats were fed through intragastric administration, the group A and B with distilled water (10 ml/kg), the group C and D respectively with suspension of colchicine tablets (10 ml/kg, 0.01 mg/ml) and water-decocted liquid of modified Qingyao decoction (10 ml/kg,1.035 g/ml), once a day and continuous medication for 18 days. All rats were killed at the 21th day after operation. The immunoglobulin G (IgG), immunoglobulin M (IgM) and interleukin-1beta (IL-1beta), interleukin-8 (IL-8) level in serum of different groups were detected by ELISA method. At the same time, surrounding tissues of the transplanted nucleus pulposus were observed by pathological section.

RESULTSThe level of IgG, IgM, IL-1beta, IL-8 in serum of group B was significantly higher than that of group A (P < 0.01), while the level of IgG, IgM, IL-1beta, IL-8 in serum of group C, D was significantly lower than that of group B (P < 0.05 or P < 0.01). Moreover, pathological section indicated that immuno-inflammatory response was hardly found in surgical site of group A, while local immuno-inflammatory response of surrounding tissues of the transplanted nucleus pulposus of group C and D was much lighter than that of group B.

CONCLUSIONRemoving dampness and promoting diuresis method could inhibit autoimmune and immuno-inflammatory response caused by nucleus pulposus of rats.

Animals ; Autoimmunity ; Disease Models, Animal ; Immunoglobulin G ; blood ; Immunoglobulin M ; blood ; Interleukin-1beta ; blood ; Interleukin-8 ; blood ; Intervertebral Disc Displacement ; immunology ; pathology ; therapy ; Lumbar Vertebrae ; Male ; Medicine, Chinese Traditional ; Rats ; Rats, Wistar

Autoimmunity ; Humans ; Immunity, Innate ; Liver Cirrhosis, Biliary ; immunology

Using directed mutagenesis and phage display on a soluble fragment of the human immunoglobulin super-family receptor ILT2 (synonyms: LIR1, MIR7, CD85j), we have selected a range of mutants with binding affinities enhanced by up to 168,000-fold towards the conserved region of major histocompatibility complex (MHC) class I molecules. Produced in a dimeric form, either by chemical cross-linking with bivalent polyethylene glycol (PEG) derivatives or as a genetic fusion with human IgG Fc-fragment, the mutants exhibited a further increase in ligand-binding strength due to the avidity effect, with resident half-times (t(1/2)) on the surface of MHC I-positive cells of many hours. The novel compounds antagonized the interaction of CD8 co-receptor with MHC I in vitro without affecting the peptide-specific binding of T-cell receptors (TCRs). In both cytokine-release assays and cell-killing experiments the engineered receptors inhibited the activation of CD8(+) cytotoxic T lymphocytes (CTLs) in the presence of their target cells, with subnanomolar potency and in a dose-dependent manner. As a selective inhibitor of CD8(+) CTL responses, the engineered high affinity ILT2 receptor presents a new tool for studying the activation mechanism of different subsets of CTLs and could have potential for the development of novel autoimmunity therapies.
Amino Acid Sequence ; Antigens, CD ; chemistry ; genetics ; pharmacology ; Autoimmunity ; Biological Assay ; Cell Line ; Cytotoxicity, Immunologic ; genetics ; immunology ; Dose-Response Relationship, Immunologic ; Humans ; Immunoglobulins ; immunology ; metabolism ; Immunologic Factors ; chemistry ; genetics ; pharmacology ; Kinetics ; Leukocyte Immunoglobulin-like Receptor B1 ; Lymphocyte Activation ; genetics ; immunology ; Major Histocompatibility Complex ; genetics ; immunology ; Molecular Sequence Data ; Molecular Targeted Therapy ; Mutagenesis, Site-Directed ; Peptide Library ; Polyethylene Glycols ; Protein Binding ; genetics ; immunology ; Receptors, Immunologic ; chemistry ; genetics ; Recombinant Fusion Proteins ; genetics ; metabolism ; T-Lymphocytes, Cytotoxic ; immunology ; metabolism