Circulating Autoantibody Profiling Identifies LIMS1 as a Potential Target for Pathogenic Autoimmunity in pathologic Myopia.

High myopia is a leading cause of blindness worldwide, among which pathologic myopia, characterized by typical myopic macular degeneration, is the most detrimental. However, its pathogenesis remains largely unknown. Here, using a HuProt array, we first initiated a serological autoantibody profiling of high myopia and identified 18 potential autoantibodies, of which anti-LIMS1 autoantibody was validated by a customized focused microarray. Further subgroup analysis revealed its actual relevance to pathologic myopia, rather than simple high myopia without myopic macular degeneration. Mechanistically, anti-LIMS1 autoantibody predominantly belonged to IgG1/IgG2/IgG3 subclasses. Serum IgG obtained from patients with pathologic myopia could disrupt the barrier function of retinal pigment epithelial cells via cytoskeleton disorganization and tight junction component reduction, and also trigger a pro-inflammatory mediator cascade in retinal pigment epithelial cells, which were all attenuated by depletion of anti-LIMS1 autoantibody. Together, these data uncover a previously unrecognized autoimmune etiology of myopic macular degeneration in pathologic myopia.

Mechanism of Chinese botanical drug Dizhi pill for myopia: An integrated study based on bioinformatics and network analysis.

To identify the active constituents, core targets, immunomodulatory functions and potential mechanisms of Dizhi pill (DZP) in the treatment of myopia. The active constituents and drug targets of DZP were searched in the TCMSP, Herb databases and correlational studies. The targets of myopia were searched in the TTD, Genecards, OMIM and Drugbank databases. Gene expression profile data of GSE136701 were downloaded from the GEO database and subjected to WGCNA and DEG analysis to screen for significant modules and targets of myopia. Intersectional targets of myopia and DZP and core targets of myopia were analyzed through the String database. The GO and KEGG enrichment analyses of the interested targets were conducted. Cibersort algorithm was used for immune infiltration analysis to investigate the immunomodulatory functions of DZP on myopia. Autodock was used to dock the important targets and active constituents. Eight targets (STAT3, PIK3CA, PIK3R1, MAPK1, MAPK3, HSP90AA1, MIP, and LGSN) and 5 active constituents (Quercetin, Beta-sitosterol, Diincarvilone A, Ferulic acid methyl ester, and Naringenin) were identified from DZP. In pathways identified by the GO and KEGG enrichment analyses, "ATP metabolic process" and "AGE-RAGE diabetes complication signaling" pathways were closely related to the mechanisms of DZP in the treatment of myopia. Molecular docking showed that both the intersectional targets and core targets of myopia could bind stably and spontaneously with the active constituents of DZP. This study suggested that the mechanisms of DZP in the treatment of myopia were related to active constituents: Quercetin, Beta-sitosterol, Diincarvilone A, Ferulic acid methyl ester and Naringenin, intersectional targets: STAT3, PIK3CA, PIK3R1, MAPK1, MAPK3, and HSP90AA1, core targets of myopia: MIP and LGSN, AGE-RAGE signaling pathway, positive regulation of ATP metabolic process pathway and immunomodulatory functions.

Novel evidence for complement system activation in chick myopia and hyperopia models: a meta-analysis of transcriptome datasets.

Myopia (short-sightedness) and hyperopia (long-sightedness) occur when the eye grows too long or short, respectively, for its refractive power. There are currently approximately 1.45 billion myopes worldwide and prevalence is rising dramatically. Although high myopia significantly increases the risk of developing a range of sight-threatening disorders, the molecular mechanisms underlying ocular growth regulation and its relationship to these secondary complications remain poorly understood. Thus, this study meta-analyzed transcriptome datasets collected in the commonly used chick model of optically-induced refractive error. Fifteen datasets (collected across five previous studies) were obtained from GEO, preprocessed in Bioconductor, and divided into 4 conditions representing early (≤1 day) and late (>1 day) myopia and hyperopia induction. Differentially expressed genes in each condition were then identified using Rank Product meta-analysis. The results provide novel evidence for transcriptional activation of the complement system during both myopia and hyperopia induction, and confirm existing literature implicating cell signaling, mitochondrial, and structural processes in refractive error. Further comparisons demonstrated that the meta-analysis results also significantly improve concordance with broader omics data types (i.e., human genetic association and animal proteomics studies) relative to previous transcriptome studies, and show extensive similarities with the genes linked to age-related macular degeneration, choroidal neovascularization, and cataract.

Rheumatic Disease Autoantibodies in Autoimmune Liver Diseases.

BACKGROUND: Autoimmune liver diseases (ALDs) are known to be associated with systemic autoimmune rheumatic diseases (SARDs) and their autoantibodies. We aimed to study the prevalence of SARDs and related autoantibodies, as well as their prognostic implications in a group of patients with ALDs. METHODS: This was a cross-sectional study. Sixty patients with ALDs (38.3% with autoimmune hepatitis; 11.7% with primary biliary cirrhosis; 25% with primary sclerosing cholangitis and 25% with overlap syndrome) were studied for the presence of SARDs and their autoantibodies. RESULTS: There was autoimmune rheumatic disease in 20% of the studied sample. Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) were the commonest (11.6% and 5%, respectively). Antinuclear antibodies (ANAs) were present in 35% of the patients, followed by anti-Ro (20.0%); anti-nucleosome (18.3%); rheumatoid factor (10%) anti-CCP (8.3%); anti-RNP (8.3%); anti-ds-DNA (6.6%); anti-La (3.3%); anti-Sm (3.3%), anti-ribosomal P (3.3%). Anti-Ro (p = 0.0004), anti-La (p = 0.03), anti-RNP (p = 0.04) and anti-Sm (p = 0.03) were commonly found in patients with SARD, but not anti-DNA, anti-nucleosome and anti-ribosomal P. No differences were found in liver function tests regarding to the presence of autoantibodies. CONCLUSIONS: There was a high prevalence of SARD and their autoantibodies in ALD patients. Anti-Ro, anti-La, anti-RNP and anti-Sm positivity points to an association with systemic autoimmune rheumatic diseases. The presence of autoantibodies was not related to liver function tests.

[Immunological graft rejection after autologous contralateral keratoplasty]. / Immunologisches Transplantatversagen nach autologer kontralateraler Keratoplastik.

Autologous keratoplasty from an amblyopic eye to the fellow oculus ultimus is a rarely used procedure. This is due to the relatively uncommon constellation of pathology. The following article reports the case of a graft rejection after autologous keratoplasty, while the homologous graft on the amblyopic fellow eye remained clear.

Pathogenic aspects of dermatomyositis, polymyositis and overlap myositis.

Inflammatory myopathies (IMs) often have distinct histopathologic features suggesting humorally mediated involvement of the microcirculation in dermatomyositis (DM), including early capillary deposition of the complement C5b-9 membranolytic attack complex (MAC) and secondary ischaemic changes; and CD8 T-cell-mediated and MHC1-restricted autoimmune attack of myofibers in polymyositis (PM) and inclusion body myositis. Novel insights in these specific diseases include emerging evidence that capillary loss involves whole microvascular units in DM, and that regulatory T-cells strongly protect myofibers from experimental autotoxic attack in PM. However, all IMs do not exhibit pathophysiology-relevant histopathologic features of DM or PM. Autoimmune necrotizing myopathies (AINM) occur in the absence of endomysial inflammatory cells and may be specifically associated with anti-SRP autoantibodies. Moreover, IM histopathological features may be scarce, unspecific and overlapping. Therefore, increasing attention is paid to features shared by IMs regardless of their type, relevant to the innate immune response and to non-immune mechanisms. Innate immune responses to myodamage (and/or as yet unknown stimuli), involves release of chemokines, activation of specific Toll-like receptors (TLRs) and complex Th-1, Th-17 and other cytokine interplays; it triggers DC recruitment and maturation, and is associated with type 1 IFN signature (especially in DM where type 1 IFN-producing cells called plasmacytoid DCs are mainly detected). Non-immune mechanisms mainly include endoplasmic reticulum (ER) stress induced in myofibers by up-regulation of MHC-class I antigens (as typically observed in PM with a diffuse pattern and in DM with perifascicular predominance). ER stress may favour autoimmune reactions but may also be associated with myofiber damage and dysfunction in the absence of lymphocytes. Overlap myositis (OM) may be associated with other connective tissue diseases and a variety of autoantibodies, such as those directed against tRNA synthetase. Myositis specific autoantibodies are mainly expressed by regenerating myofibers, that may also express MHC-1 and endogenous ligand-binding TLRs, thus drawing a picture in which the regenerating myofiber plays a central pathophysiologic role.

Relationship between myopia and allergen-specific serum IgE levels in patients with allergic conjunctivitis.

PURPOSE: Various exogenous allergens can cause allergic conjunctivitis, whereas refractive errors are also related (as an endogenous factor) to the pathogenesis of allergic conjunctivitis. However, little is known about the interaction between exogenous and endogenous factors in patients with allergic conjunctivitis. We investigated the relationship between refractive errors and exogenous allergens in patients with allergic conjunctivitis. METHODS: Sixty patients with allergic conjunctivitis and 60 healthy subjects (non-allergy patients) were enrolled. Refraction was carried out in all subjects. In addition, total immunoglobulin E (IgE) and specific IgE levels for 12 inhaled allergens were measured by the capsulated hydrolic carrier polymer system. RESULTS: The patients who were positive for-specific IgE to indoor allergens had higher myopia than those who were negative, including those positive for house dust IgE (-3.66 +/- 2.95 vs. -1.05 +/- 3.39, P = 0.0015), Dermatophagoides pteronyssinus (D. pteronyssinus) IgE (-3.50 +/- 2.91 vs. -1.01 +/- 3.46, P = 0.0021), and acarus IgE (-3.45 +/- 2.21 vs. -1.51 +/- 3.73, P = 0.0087), whereas antibody-positive and antibody-negative patients for outdoor allergens showed no significant differences of refraction. Refractions in indoor group (-3.58 +/- 3.42) and indoor/outdoor (-3.70 +/- 2.64) group were higher than those in outdoor group (-0.84 +/- 2.30, P = 0.0047 and P = 0.0032) and the non-allergy group (-1.30 +/- 1.48, P = 0.0082 and P = 0.0054) [-refraction] was significantly correlated with total IgE (r = 0.333, P = 0.0093), house dust (r = 0.355, P = 0.0054) and D. pteronyssinus (r = 0.379, P = 0.0028), while no correlation between refractive error and outdoor allergens was proven. CONCLUSION: These results suggest that specific IgE levels for indoor allergens, such as house dust, might be associated with refractive errors.

Risk for uveitis after laser in situ keratomileusis in patients positive for human leukocyte antigen-B27.

PURPOSE: To assess the incidence of, risk for, and visual outcomes of acute anterior uveitis (AAU) in human leukocyte antigen (HLA)-B27 positive patients who had laser in situ keratomileusis (LASIK). SETTING: University-based center. METHODS: This study comprised 46 eyes of 23 HLA-B27 positive patients with a 5-year follow-up. Data on episodes of uveitis were reviewed retrospectively and the incidence rates calculated for LASIK and non-LASIK eyes. Kaplan-Meier survival probabilities were calculated for uveitis occurring during the final 36 to 60 months of the study. Survival probabilities between LASIK and non-LASIK eyes were compared. RESULTS: Twenty eyes (10 patients) had LASIK a mean of 36 months+/-2 (SD) after the diagnosis of HLA-B27. In the HLA-B27 positive patients, the incidence rates of uveitis between eyes that had and eyes that did not have LASIK were not significantly different. The incidence rates of uveitis after LASIK did not differ significantly between eyes with and eyes without episodes of uveitis before LASIK (P=.135). The probability of an eye having no episode of uveitis in the fourth and fifth year of follow-up was not significantly different between eyes that had LASIK and those that did not (P=.668). CONCLUSIONS: The occurrence rate of post-LASIK AAU in the HLA-B27 positive population was not higher than the general incidence in a similar HLA-B27 population without previous LASIK. A previous episode of uveitis did not appear to increase the risk for uveitis after LASIK in HLA-B27 positive patients.

[State of the neurodynamic and immune system in people with myopia].

State of the neyrodynamic functions and the immune system under moderate myopia that is considered as organism adaptation to the emotional-informative stress was the purpose of our research. It was established that moderate myopia is accompanied by the functional tension of the immune systems, namely by the secondary immunodeficiency of the cellular part, with an improvement of indexes of neurodynamic functions (functional mobility of nervous processes). The positive correlation between functional mobility of nervous processes and the amount of monocytes in a peripheral blood was shown (r = 0.7). The same interrelation was established between functional mobility of nervous processes and the amount of T-suppressors in a peripheral blood (r = 0.6).

[A preliminary study on the association between HLA-DPB1 gene and pathological myopia].

OBJECTIVE: To investigate the association between distribution of human leucocyte antigen class II DPB1 alleles and pathological myopia (PM) among Chinese. METHODS: The second exons of the HLA-DPB1 genes of 40 patients with PM were amplified by polymerase chain reaction (PCR), individual PCR products were digested by allele specific restriction enzymes: Bsp 1296 I, Fok I, Dde I, BsaJ I, BssH II, Rsa I, Ava II and EcoN I. Genotype of each patient was determined by restriction fragment length polymorphism (RFLP) pattern, then each DPB1 allele frequency of PM was calculated and compared with healthy control. RESULTS: The frequency of DPB1*0301 allele was significantly decreased in PM (Yates corrected chi 2 = 4.33, Fisher exacted P = 0.032 < 0.05) and no statistically significant difference was observed after P value was corrected by the number of compared alleles. The rate of DPB1*0501/0501 homozygote has a significant difference between PM and healthy controls (u = 2.27, P < 0.05). CONCLUSIONS: No genetic susceptible or resistant allele exists in HLA-DPB1 gene of PM. The significant increase of DPB1*0501/0501 homozygote in PM may be a linkage information.

[Clinical-immunological and epidemiological studies in high complicated myopia]. / Kliniko-immunologicheskie i épidemiologicheskie issledovaniia pri vysokoi oslozhnennoi miopii.

A total of 100 patients with high complicated myopia were examined. Immunodeficiency syndrome and signs of autosensitization were revealed in this patient population. Analysis of morbidity and its relationship with some environmental factors and characteristics of the activity of public health system showed that the morbidity was related to increased radioactivity and to unsatisfactory status of water in a region, and that increase of the number of medical workers may help reduce the morbidity.

[Study of immune reactions to collagen in patients with myopia]. / Issledovanie immunnoi reaktsii na kollagen u bol'nykh s miopiei.

Fifty-five blood sera and twenty-three samples of lacrimal fluid of patients with medium and high myopia were tested for antibodies to the main structural protein of the sclera, collagen, by enzyme immunoassay. Serum autoantibodies to collagen were detected in 50-70% of patients with all forms of myopia (congenital, early acquired, and acquired at school age). Antibodies to collagen were not detected in the lacrimal fluid, which was regarded as an evidence of the predominance of systemic autoimmune reactions. Antibody titers were the highest in the blood sera of patients with uncomplicated and slowly progressing myopia. Rapidly progressing myopia complicated by mixed forms of peripheral vitreo-chorioretinal dystrophies, including ruptures of the retina, was characterized by a deficit of antibodies to collagen in the blood serum. This implies a possible protective role of antibodies to collagen detected in the blood of patients with myopia. These results are regarded as a proof in favor of the participation of autoimmune reactions to collagen in the pathogenesis of medium and high myopia.

Trichinosis with severe myopathic involvement mimicking polymyositis. Report of a family outbreak.

We describe an outbreak of trichinosis in 3 members of a rural family. In the 3 patients eating raw pork was the source of infection. They presented with myalgias and severe proximal muscle weakness mimicking polymyositis. The diagnosis was made by demonstration of larvae of Trichinella spiralis in the muscle biopsy and also by the presence of anti-Trichinella antibodies detected by double immunodiffusion in their sera. We call attention to the unusual clinical presentation of trichinosis in our patients that was manifested by severe muscle weakness that may be confused with polymyositis.

[Circulating immune complexes in the blood and anterior chamber fluid in patients with glaucoma and diabetic angioretinopathy complicated by myopia and senile cataract]. / Tsirkuliruiushchie immunnye kompleksy v syvorotke krovi i vlage perednei kamery glaza u bol'nykh glaukomoi, diabeticheskoi angioretinopatiei, oslozhnennoi blizorukost'iu i vozrastnoi kataraktoi.

Circulating immune complexes (CIC) in the serum and anterior eye chamber were simultaneously measured by 4% polyethylene glycol in 23 ophthalmologic patients. The patients with noncomplicated cataracts were found to have elevated serum levels of CIC (175 +/- 8.1 opt. units, p less than 0.001), whereas the patients with glaucoma, diabetic angioretinopathy, and complicated myopia had even higher CIC levels in the serum (247 +/- 7.1 opt. units, p less than 0.001) together with the increased CIC levels in the anterior eye chamber fluid (29.43 +/- 0.88 opt. units, p less than 0.001), which fact is indicative of the augmentation of the autoimmune component it the progress of the dystrophic changes in the eye tissues.

[Clinico-immunologic aspects of development of cataracts in patients with myopia]. / Izuchenie kliniko-immunologicheskikh aspektov obrazovaniia katarakty u bol'nykh s miopiei.

The present study has been aimed at the detection of specific antibodies to the lens and its capsule in the circulating blood of patients with complicated myopic cataracts. The presence of these antibodies results in the development of the posterior capsule fibrosis, this leading to the migration of the cells from the equatorial area to the site of the capsule injury. The detection of the specific antibodies in the blood will help single out the risk group among the patients for whom implantation of a negative intraocular lens is indicated for the correction of high myopia. The presence of these antibodies may also help predict the development of a cataract in the postoperative period; besides, it may be used to create an immunological certificate, informing on the presence of antibodies specific for the lens or its capsule in the patient's circulating blood.