Infections In Autoimmune Diseases Research Articles

Is Toxoplasma gondii infection protective against multiple sclerosis risk?

BackgroundParasitic infections may play a protective role in neurodegenative diseases. ObjectıveTo determine the association between Toxoplasma gondii (T. gondii) infection and Multiple Sclerosis (MS). MethodsOne hundred fifteen patients with MS were included in the study. Sixty age and gender-matched healthy subjects were recruited as controls. Subjects were assessed for clinical and demographic parameters. The presence of specific IgG antibodies against T. gondii microorganism was searched by using an enzyme immunoassay test in the sera of the subjects. ResultsT. gondii seropositivity was found to be lower in MS patients than in healthy controls (33.9% vs. 55%, p=0.007). Mean age and disease duration of the patients were 41.15±11.20 (18–74) and 1.90±1.44 (0–6) years, respectively. MS patients with a high IgG titer had lower expanded disability status scale (EDSS) scores (p=0.001) and lower annualized relapse rates (ARR) (p=0.005). There was no significant association between T. gondii seropositivity and disease duration (p=0.598). Female MS patients tended to have higher T. gondii seropositivity than males although the difference did not reach statistical significance (p=0.192). We found a negative correlation between T. gondii seropositivity and both EDSS scores (r=−0.322, p<0.001) and ARR (r=−0.263, p=0.004). ConclusıonWe found a negative association between T. gondii infection and the presence of MS. Furthermore, parasite infected MS patients had experienced fewer relapses with lower disability scores supporting the hypothesis of immunomodulatory effects of parasitic infections in autoimmune diseases. Further studies are required to establish the protective role of parasitic infections in MS.

Optimization of Immunosuppression and the Prevention of Fungal Infection in Autoimmune Diseases

Mycophenolate mofetil (MMF) has recently been reported to be effective in the treatment of systemic lupus erythematosus (SLE). The therapeutic range of mycophenolic acid (MPA) and its 7-O-glucuronide (MPAG), and factors affecting their pharmacokinetics, remain to be clarified. The influence of the pharmacokinetics of MPA and MPAG on the activity of inosine 5'-monophosphate dehydrogenase (IMPDH), a target of the MPA, also remains to be revealed. The pharmacokinetic variability of hydroxy-itraconazole (OH-ITZ), an active metabolite of itraconazole frequently co-administered with immunosuppressants in immunocompromised patients, is not fully known. The aim of this study was to establish the optimal dosage and administration of immunosuppressants and antifungal agents. MMF improved clinical laboratory markers and reduced prednisolone dosage in 31 SLE patients, with a pre-dose plasma concentration of MPA and MPAG in the interquartile ranges of 0.94-2.96 and 18.6-53.7 μg/mL, respectively. Renal function and co-administered metal influenced the pharmacokinetics of MPA and MPAG in 31 SLE patients in the remission maintenance phase. IMPDH activity was induced in 29 SLE patients receiving the MMF therapy. This induction was dependent on the plasma concentration of MPAG, but not MPA. In addition, IMPDH activity was negatively correlated with complement fraction C3. MPA exposure and disease activity in SLE patients may determine IMPDH activity. The pharmacokinetic variability of OH-ITZ was associated with saturated metabolism to keto-itraconazole, serum concentration of albumin, and renal function in 46 immunocompromised patients. Prevention of fungal infections and drug-drug interactions in immunocompromised patients can be obtained by considering these identified confounding factors.

Potential Role of Bacterial Infection in Autoimmune Diseases: A New Aspect of Molecular Mimicry

Molecular mimicry is an attractive mechanism for triggering autoimmunity. In this review, we explore the potential role of evolutionary conserved bacterial proteins in the production of autoantibodies with focus on granulomatosis with polyangiitis (GPA) and rheumatoid arthritis (RA). Seven autoantigens characterized in GPA and RA were BLASTed against a bacterial protein database. Of the seven autoantigens, proteinase 3, type II collagen, binding immunoglobulin protein, glucose-6-phosphate isomerase, α-enolase, and heterogeneous nuclear ribonuclear protein have well-conserved bacterial orthologs. Importantly, those bacterial orthologs are also found in human-associated bacteria. The wide distribution of the highly conserved stress proteins or enzymes among the members of the normal flora and common infectious microorganisms raises a new question on how cross-reactive autoantibodies are not produced during the immune response to these bacteria in most healthy people. Understanding the mechanisms that deselect auto-reactive B cell clones during the germinal center reaction to homologous foreign antigens may provide a novel strategy to treat autoimmune diseases.

Role of helicobacter pylori infection in autoimmune diseases

The etiology of most autoimmune diseases remains elusive. Prevailing evidence suggests an environmental trigger in a genetically susceptible individual. Helicobacter pylori (H. pylori) have managed to survive in a hostile environment in their host for long period and have evaded eradication by the immune system. Its chronic interaction with the immune system and the ubiquitous presence worldwide makes H. pylori an ideal candidate to study as a trigger of autoimmune phenomena. In this review, we would present data regarding the interplay between H. pylori and various components of the immune system and its association with various autoimmune diseases. Strong associations of H. pylori with some autoimmune diseases such as immune thrombocytopenia have been found; but most other autoimmune disease studies have revealed conflicting data. The chronic survival of H. pylori in humans is possible because of an overall downregulation of the body's immune response. In addition to this overall effect on the immune system, there are clinical and epidemiological data suggestive of H. pylori infection having a protective role in some autoimmune diseases. Based on our review H. pylori status should be checked and treated only in certain autoimmune diseases such as ITP. For the majority of the autoimmune diseases, the role of H. pylori remains controversial signifying need for further research.

Anti-TNFs and severe infections in autoimmune diseases: The other side of the coin

Anti-TNFs and severe infections in autoimmune diseases: The other side of the coin

Prior elevation of IL‐18 promotes rapid early IFN‐γ production during staphylococcal infection

Systemic Staphylococcus aureus infection is associated with significant morbidity and mortality arising from both bacterial and host immune factors. IL-18 is a pro-inflammatory cytokine of the IL-1 superfamily that exhibits broad functional effects in innate and acquired immune responses and which has been found in high levels in several chronic inflammatory and autoimmune diseases. Over-expression of IL-18 may promote early resolution of infection or could promote a detrimental exaggerated immune response. This was explored in a model of S. aureus infection. We report increased mortality in Swiss mice that were given recombinant IL-18 prior to inoculation with S. aureus LS-1. IL-18 administration prior to infection induced preferentially enhanced IFN-gamma mRNA expression in peripheral blood leukocytes and spleen, especially splenic NK cells. This correlated with increased IFN-gamma protein detection in serum, and leukocyte and spleen cultures at subsequent discrete time points. These data suggest that increased mortality following gram-positive infection in autoimmune diseases could in part reflect the impact of high levels of pleiotropic pro-inflammatory cytokines such as IL-18 present prior to the onset of infection.