Effect of serum metabolites on the risk of iridocyclitis: a bidirectional Mendelian randomization study.

Previous research has linked serum metabolite levels to iridocyclitis, yet their causal relationship remains unexplored. This study investigated this potential causality by analyzing pooled data from 7824 iridocyclitis patients in a Genome-Wide Association Study (GWAS) using Mendelian randomization (MR) and linkage disequilibrium score regression (LDSC). Employing rigorous quality control and comprehensive statistical methods, including sensitivity analyses, we examined the influence of 486 serum metabolites on iridocyclitis. Our MR analysis identified 23 metabolites with significant causal effects on iridocyclitis, comprising 17 known and 6 unidentified metabolites. Further refinement using Cochran's Q test and MR-PRESSO indicated 16 metabolites significantly associated with iridocyclitis risk. LDSC highlighted the heritability of certain metabolites, underscoring genetic influences on their levels. Notably, tryptophan, proline, theobromine, and 7-methylxanthine emerged as risk factors, while 3,4-dihydroxybutyrate appeared protective. These findings enhance our understanding of the metabolic interactions in iridocyclitis, offering insights for diagnosis, unraveling pathophysiological mechanisms, and informing potential avenues for prevention and personalized treatment.

Causal analysis of serum polyunsaturated fatty acids with juvenile idiopathic arthritis and ocular comorbidity.

BACKGROUND & OBJECTIVE: To investigate the causal effects of plasma Polyunsaturated fatty acids (PUFAs) on the risk of juvenile idiopathic arthritis (JIA) and ocular comorbidity through Mendelian randomization (MR) analysis. METHODS: Genetic variants (formerly single nucleotide polymorphisms, SNPs) that are strongly associated with PUFAs levels (P < 5×10-8) were selected as instrumental variables. Summary-level MR was performed with outcome estimates for JIA (n = 31,142) and JIA associated iridocyclitis (n = 94,197). The inverse variance-weighted (IVW) method was employed as the main approach to combine the estimation for each SNP. Two set of models with summary statistics were conducted and multiple sensitivity analyses were applied for testing of pleiotropic bias. RESULTS: In model 1, genetically predicted n-6 PUFAs linoleic acid (LA) and arachidonic acid (AA) were associated with lower and higher risk of JIA associated iridocyclitis using IVW (ORLA = 0.940, 95% CI: 0.895-0.988, P = 0.015; ORAA = 1.053, 95% CI: 1.007-1.101, P = 0.024). No such association was observed between each plasma PUFAs and JIA susceptibility (P > 0.05). In further MR analysis, results from model 2 also showed a consistent trend. Besides, multiple sensitivity analyses revealed that there was no obvious evidence for unknown pleiotropy (P > 0.05). CONCLUSIONS: Our MR study provides genetic evidence on the possible causality that plasma LA level might protect against JIA associated iridocyclitis, whereas AA was responsible for opposite effect.

[Characteristics of inflammatory response in patients after senile cataract surgery].

The aim of the work was to study prognostic value of some laboratory markers (anti-DNA antibodies, cell adhesive molecules, neopterin) in heriatric patients with exudative inflammation after cataract surgery. 12 in-patients with postoperative iridocyclitis and endophthalmitis were included. The assays were taken twice: after admission and before discharging. The follow-up period was 6 months. Preliminary data show that high serum levels of sVCAM, sICAM and anti-DNA antibodies, as well as very low levels of anti-DNA antibodies seems to be associated with poor outcomes in those patients (enucleation, blindness, lens extraction). Small cohort doesn't allow us to make strict conclusion about prognostic value of these laboratory markers. The study should be continued.

[Endotoxin Is a Companent in Pathogenesis of Chronic Viral Diseases].

The level of endotoxin and indicators of activity of antiendotoxin immunity (antibody concentration to glycolipid Re-chemotype and general antigen of enterobacteria) were estimated in serum of 174 patients with persistent viral infections (viruses: herpes simplex, hepatitis C, human immunodeficiency). The presence of markers of systemic inflammatory response syndrome (interleukin IL-1ß) and acquired immunodeficiency (CD4+) in HIV-infected patients were also determined. Persistent viral infections are accompanied by endotoxin aggression intestinal origin (caused by them), which is able to induce the development of systemic inflammatory response syndrome. In HIV-infected patients with this syndrome is cyclical, when the phase of hyperactivity replaced immunodeficiency. Schematically, this process can be represented as the following sequence of events: HIV-mediated damage to the intestinal barrier--the development of endotoxin aggression--induction ofsystemic inflammatory response syndrome--the depletion of the immune system, which is transient and is related to the duration of activity of the virus replication cycle, i.e., with damage to enterocytes. Using antiendotoxin component (means of reducing levels of endotoxin in the blood) in the scheme of treatment of persistent viral infections can serve as an element of a successful prevention of complications.

Rubella virus as a possible etiological agent of Fuchs heterochromic iridocyclitis.

BACKGROUND: To determine whether rubella virus is involved in the pathogenesis of Fuchs heterochromic iridocyclitis (FHI). METHODS: Fourteen patients (14 eyes) diagnosed with FHI based on characteristic ocular manifestations and eight control subjects were studied. Aqueous humor (AH) samples from 14 FHI patients and one vitreous sample from a FHI patient were analyzed for intraocular antibody production against rubella virus by calculation of the Goldmann-Witmer coefficient (GWC). Viral detection by nested polymerase chain reaction and isolation by culture in RK-13 cells were conducted in nine FHI patients. In addition to laboratory examinations, medical history of rubella virus vaccination was also obtained. RESULTS: Ten patients with FHI examined showed intraocular synthesis of rubella virus antibodies (GWC > 3). A high index of rubella virus antibody production was also found in the vitreous sample (GWC = 30.6). GWC in all control subjects were below detectable level. The rubella genome was detected in two of nine patients, and rubella virus was isolated from one of nine patients with FHI. None of the patients with FHI had been vaccinated against rubella. CONCLUSIONS: Our laboratory data strongly suggest a relationship between FHI and rubella virus.

Peripheral vascular endothelial dysfunction in glaucomatocyclitic crisis: a preliminary study.

PURPOSE: Glaucomatocyclitic crisis (GCC) is a syndrome of recurrent unilateral increased intraocular pressure associated with mild cyclitis and few clinical symptoms. This study was undertaken to assess brachial artery endothelium-dependent flow-mediated vasodilation (FMD) as an indicator of vascular endothelial function, to describe the association between GCC and endothelial dysfunction excluding age effects. METHODS: This prospective study was conducted from January 2007 to April 2009 and included 12 patients with GCC and 15 age-matched normal control subjects. Detailed clinical parameters were reviewed, including highly sensitive C-reactive protein (hs-CRP), homocysteine, anti-SSA, anti-cardiolipin antibodies, and HLA type. Brachial artery FMD and endothelium-independent, nitroglycerin-mediated vasodilation (NMD) were studied by using high-resolution, two-dimensional (2-D) ultrasonic imaging. RESULTS: Twelve patients with GCC were evaluated. The mean age of the patients was 36.3 years including 5 (41.6%) women and 7 (58.4%) men. There were no significant differences between patients with GCC and control subjects with regard to basal data, including body mass index, smoking, blood pressure, complete blood count, and routine blood biochemistries. Homocysteine and hs-CRP were within normal limits. Two (16.7%) patients were positive for HLA-B27, anti-SSA, and anti-cardiolipin antibodies. The nitroglycerin-mediated vasodilation in the patients with GCC was not significantly different from that of the control group. The FMD was much lower in the GCC group than in the control groups (mean 4.81% vs. 7.89%, P < 0.01). CONCLUSIONS: The significantly lower FMD in patients with GCC implies peripheral vascular endothelial dysfunction. However, in the 16.7% positive for the HLA-B27, anti-SSA, and anti-cardiolipin antibodies, these parameters are associated with GCC and abnormal FMD.

[Intestinal endotoxin in the pathogenesis of ocular inflammatory diseases and the antiendoxin constituent of its treatment].

Blood was studied in 119 patients with ocular inflammatory lesions: endophthalmitis (n = 10), iridocyclitis of viral (n = 47) and unknown (n = 62) genesis, by using the procedures developed by the authors to determine the integral values of the concentration of endotoxin in systemic blood flow and the activity of antiendotoxin immunity. Intestinal endotoxin aggression was found to be involved in the pathogenesis of ocular inflammatory diseases. The use of drugs and procedures, which could diminish the entry of intestinal endotoxin into the blood stream and intensify the processes of its binding and release from systemic blood circulation, substantially enhanced the efficiency of a therapeutic process.

Soluble HLA class I and HLA-DR plasma levels in patients with anterior uveitis.

Anterior uveitis (AU) is an autoimmune disease frequently associated with HLA-B27 antigen. Because of the immune regulatory properties of soluble human leukocyte antigen (sHLA) molecules, we quantified sHLA class I (sHLA-I) and sHLA-DR plasma levels in HLA-typed AU patients (n = 60). Randomly selected healthy individuals (n = 128) and HLA-B27 antigen-positive individuals (n = 24) with HLA phenotype frequencies similar to the HLA-B27 antigen-positive AU patients served as control panels. As expected, HLA-B27 phenotype was significantly increased in AU patients (n = 60), compared to healthy controls. Mean sHLA-I levels in AU patients were slightly higher than in randomly selected healthy controls. Regarding AU subgroups, elevated sHLA-I levels were only found in HLA-B27 antigen-negative patients. Compared to controls, sHLA-DR levels were significantly increased in AU patients and the subgroups of HLA-B27 antigen-negative and -positive patients but not Fuchs' heterochromic cyclitis (FHC). AU patients negative for HLA-B27 antigen with a chronic course had higher sHLA-DR levels than those with an acute course. The presence of associated systemic diseases in AU patients was related to elevated sHLA-DR levels. Secretion of sHLA-DR in blood differs among the various forms of AU. Systemic immune activation was present in AU but not in FHC.

[An express-method for predicting fibrinous iridocyclitis in the early postoperative period in artiphakia]. / Ekspress-metod prognozirovaniia gibrinoznogo iridotsiklita v rannem posleoperatsionnom periode pri artifakii.

The authors investigated the possibility of using the level of preoperative blood monocytosis as an express method for predicting fibrinous iridocyclitis in planned artiphakia. Extracapsular cataract extraction with intraocular correction (B. N. Alexeev's design) was carried out in 372 patients, 287 of these without non-insulin-dependent diabetes mellitus (NIDDM) (group 1) and 85 with NIDDM (group 2). The patients were divided into 3 subgroups depending on the absolute blood monocyte counts before operation: 1) up to 200 monocytes, 2) 200-400, and 3) more than 400. The incidence of fibrinous iridocyclitis was significantly higher (p < 0.01, 17-18-fold on average) in both subgroups 3 (more than 400 monocytes) in comparison with subgroups 1 (less than 200 monocytes), the treatment strategy being the same in all patients. In NIDDM group the total number of fibrinous iridocyclitis cases was 2 times higher in all 3 subgroups than in group 1. Hence, the level of preoperative blood monocytosis can be used as an express method for predicting fibrinous iridocyclitis in planned artiphakia choosing the treatment strategy during the immediate postoperative period, including that for patients with NIDDM.

Increase of macrophage migration inhibitory factor in sera of patients with iridocyclitis.

AIMS: To determine whether macrophage migration inhibitory factor (MIF) levels were increased in sera of the patients with iridocyclitis. METHODS: Sera were obtained from 41 patients with acute iridocyclitis, 13 patients with chronic iridocyclitis, and 44 healthy control subjects. MIF levels were determined by a human MIF ELISA. RESULTS: The average levels of MIF in the sera of patients with both acute and chronic iridocyclitis were significantly higher than that of healthy subjects. CONCLUSION: Uveitis induces the elevation of serum MIF, which may affect various inflammatory symptoms in uveitis.

Tissue plasminogen activator to treat impending pupillary block glaucoma in patients with acute fibrinous HLA-B27 positive iridocyclitis.

PURPOSE: To report the use of intracameral tissue plasminogen activator to dissolve fibrinous membranes and break posterior synechiae in patients with acute HLA-B27-positive iridocyclitis with impending pupillary block. METHODS: Two patients with severe acute fibrinous iridocyclitis and seclusio pupillae were identified. Because of the concern of impending pupillary block, intracameral tissue plasminogen activator (12.5 microg in 0.1 ml, Activase; Genentech, Inc, South San Francisco, California) was injected with a 25-gauge needle through the corneal limbus. RESULTS: Both patients showed complete dissolution of fibrin with disruption of posterior synechiae. There were no adverse events after injection. Neither patient required further invasive intervention, and both fully recovered with medical management. CONCLUSIONS: Intracameral tissue plasminogen activator is a safe and effective agent for patients with severe acute iridocyclitis and pupillary seclusion. Patients with clinical signs suggestive of impending pupillary block glaucoma may be considered for tissue plasminogen activator injection to avoid the possible need for emergency surgical iridectomy and synechiolysis.

HLA class II alleles and heterogeneity of juvenile rheumatoid arthritis. DRB1*0101 may define a novel subset of the disease.

OBJECTIVE: To examine the distribution of HLA class II alleles in clinically distinct juvenile rheumatoid arthritis (JRA) subsets. METHODS: We typed 298 patients and 181 controls for HLA-DRB1, DQA1, DQB1, and DPB1 alleles using polymerase chain reaction and oligonucleotide probe techniques. RESULTS: Each JRA subset was characterized by a distinct distribution of HLA class II alleles. For the persistently pauciarticular and rheumatoid factor-negative polyarticular JRA subsets, certain combinations of DRB1 and DPB1 alleles were characteristic. In patients without antinuclear antibodies and chronic iridocyclitis, there was an increase of DRB1*0101/02 and DQA1*0101. CONCLUSION: Findings of HLA typing support clinical subdivisions of the disease and suggest the existence of a novel DRB1*0101/02 and DQA1*0101 associated disease subset.

Elevated serum sialic acid in idiopathic acute iridocyclitis.

We measured the serum levels of sialic acid in 12 patients with idiopathic acute iridocyclitis and 18 normal controls. Sialic acid levels were significantly elevated in the patients with idiopathic acute iridocyclitis. Since animal studies have shown that intraocular inflammation alone cannot elevate serum level of sialic acid, the result of our study suggest that idiopathic acute iridocyclitis may be a multiorgan disease with systemic effects.

Circulating ICAM-1 levels in serum of uveitis patients.

Intercellular Adhesion Molecule-1 (ICAM-1) is a cytokine-inducible adhesion molecule expressed on cells of multiple lineages at sites of inflammation. Recently a truncated form of ICAM-1 has been discovered to be circulating in serum. This study reports on circulating serum (cICAM-1) levels in 132 uveitis patients (HLA-B 27 pos. acute anterior uveitis (AAU); HLA-B27 neg. anterior uveitis (AU); intermediate uveitis (IU); heterochromic cyclitis Fuchs (HCF); sarcoidosis; Toxoplasmosis). Measurement of circulating ICAM-1 serum levels was performed using a monoclonal antibody based ELISA, with healthy blood donors serving as the control group. Applying multiple variance analysis and the Student Newmann-Keuls test we found a statistically significant elevation of serum cICAM-1 level in the HLA-B 27 neg. AU group (n:31), in the IU group (n:25) and in patients with sarcoidosis (n:18). Serum levels of HLA-B27 pos. AAU patients, patients with HCF and patients suffering from ocular toxoplasmosis did not differ significantly from levels of the control group.