Presence Of Systemic Autoimmune Disease Research Articles

Cardiovascular events risk in patients with systemic autoimmune diseases: a prognostic systematic review and meta-analysis.

Chronic inflammation is considered a risk factor for the development of atherosclerosis and cardiovascular (CV) events. We seek to assess the risk of CV events in patients with Systemic autoimmune diseases (SAD), such as Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), Psoriasis (Ps) and Ankylosing Spondylitis (AS), compared with the general population. A systematic search of MEDLINE from inception up to May 2021 was performed. Observational studies including individuals with and without autoimmune diseases (SLE, RA, Ps, AS), which reported a measure of association and variability for the effect of SAD on CV events, were included. The random effects meta-analysis was performed using the Hartung-Knapp-Sidik-Jonkman approach to obtain the pooled estimates. Cardiovascular Events including CV mortality, non-fatal myocardial infarction (MI), non-fatal stroke and coronary revascularization were the main outcomes evaluated. Fifty-four studies were selected, with a total of 24,107,072 participants. The presence of SAD was associated with an increased risk of CV mortality (HR 1.49 [95% CI 1.10-2.03]), non-fatal MI (HR 1.42 [95% CI 1.23-1.62]), and non-fatal stroke (HR 1.47 [95% CI 1.28-1.70]). RA, SLE, and Ps (particularly with arthritis) were significantly associated with a higher risk of MI and stroke. SAD was also associated with an increased risk of Major Adverse Cardiovascular Events (MACE) (HR 1.45 [95% CI 1.16-1.83]). Patients with SAD present an increased risk of CV morbidity and mortality, which should be considered when establishing therapeutic strategies. These findings support the role of systemic inflammation in the development of atherosclerosis-driven disease.

Coeliac disease is a risk factor for the development of seronegative arthritis in patients with autoimmune thyroid disease.

Hashimoto's thyroiditis is known to cluster with other systemic autoimmune disorders. Rheumatic manifestations, such as a seronegative non-erosive polyarthritis have been described. The aim of this study was to evaluate the characteristics and the prevalence of rheumatic features in thyroiditis patients, and to ascertain whether the association with systemic autoimmune disorders improved the arthritis manifestations. In total, 180 thyroiditis patients were enrolled. Major clinical and demographic characteristics have been recorded. Patients underwent a rheumatological clinical assessment and extra-articular manifestations allowing for a differential diagnosis with systemic autoimmune diseases and spondyloarthropathy. Presence of systemic autoimmune diseases was recorded. A total of 8.33% of thyroiditis patients shown a peripheral inflammatory arthritis (P = 0.002). Female gender (P = 0.042) and thyroid peroxidase (TPOAbs) positivity (P = 0.001) were more frequent. In total, 37 patients had systemic autoimmune diseases (P = 0.0003). A significant high prevalence of coeliac disease and Addison disease was found (P = 0.034 and P = 0.049, respectively). In patients with coeliac disease, the articular manifestations were more frequent (21.21%) (P = 0.001) and the risk to develop joint involvement was 2.96. Although we found an articular involvement in about one-third of thyroiditis patients, the prevalence of inflammatory arthropathy was only 8.33%. The prevalence of other coexisting autoimmune disorders was 34.26% with a significant prevalence of coeliac disease (7.41%). Thyroiditis patients with coeliac disease have an articular involvement more frequently than those without. In these patients, we have found a high risk of developing arthritis than patients with only thyroiditis, suggesting cumulative autoimmune effects in the developing articular involvement.

Autoimmune vertigo: an update on vestibular disorders associated with autoimmune mechanisms.

The role of the immune system in mediating cochleovestibular pathologies has received increasing attention in recent years. Autoimmune vertigo may be an invalidating condition and may worsen the quality of life of affected patients, especially in the cases of delayed diagnosis. Since the etiopathogenesis is still not clear, also the treatment is not yet completely delineated. According to the clinical presentation, autoimmune vertigo can present as an isolated disorder or in association with systemic autoimmune diseases. The main feature in autoimmune vertigo is the presence of an abnormal immune response, in either absence or presence of systemic autoimmune disease, directed against delicate components of the inner ear. This may determine a functional or anatomical alteration, with an inflammatory reaction often devastating for hearing and balance. Being the exact pathogenesis unknown, the diagnosis of autoimmune vertigo is based either on clinical criteria or on a positive response to steroids. The earlier the diagnosis is made, the sooner the therapy can be installed, giving a chance to the recovery of inner ear damages. Corticosteroids represent the most effective and universally accepted treatment, even if other immunomodulatory drugs are now having a more extensive use. HIGHLIGHTS: Vertigo is relatively frequent in autoimmune diseases; however, it is often misdiagnosed or attributed to central nervous system alterations rather to specific inner ear involvement. Vertigo and other audiovestibular symptoms may be the first manifestation of an autoimmune disease and if correctly addressed could significantly contribute to early diagnosis of the underlying autoimmune disease. Early diagnosis of immune-related vertigo can lead to prompt initiation of targeted therapy with elevate chances of preventing irreversible damages to the inner ear. The presence of alternating phases of well-being and disabling symptoms in patients with vertigo should always been considered, as they could suggest an underlying autoimmune condition.

Uveitis in Siriraj Hospital: pattern differences between immune-related uveitis and infectious uveitis in a university-based tertiary care hospital.

To describe a proportion of uveitis and to analyse differences between immune-related uveitis and infectious uveitis groups. A retrospective study of 458 uveitis patients were categorized into immune-related uveitis, infectious uveitis, masquerade, and undetermined groups. The pattern of inflammation was described. Subgroup analysis was performed to compare pattern differences between immune-related uveitis and infectious uveitis groups. The most common location of inflammation was the anterior eye segment. Vogt-Koyanagi-Harada disease was the most common identifiable cause. From multivariate analysis, variables found to be significantly different between immune-related uveitis group and infectious uveitis group were age of onset, presence of systemic autoimmune diseases, HIV infection, and laterality. Idiopathic anterior uveitis was the most prevalent diagnosis. Vogt-Koyanagi-Harada disease was the most common identifiable uveitis. Most immune-related uveitis patients were young and presented with chronic bilateral panuveitis, with most patients in the infectious uveitis group presenting with chronic unilateral posterior uveitis.

Procoagulant Profile in Primary Antiphospholipid Syndrome Is Not Dependent upon Increased Inflammatory Response

The association of systemic inflammation and thrombosis in antiphospholipid syndrome (APS) is a matter of debate. The "second hit" theory advocates that the immune-mediated activation of endothelial cells, platelets and monocytes is the stimulus which triggers the initial pathogenesis of APS, while a second stimulus would be necessary for the onset of thrombosis. According to the theory, inflammation and hypercoagulability are not necessarily correlated and the latter would be the result of other associated factors in APS. Further clinical evidences may support that theory, since patients with venous thromboembolism without antiphospholipids (VTE-non aPL) may present an inflammatory state without the aggressive and recurrent thrombotic presentation observed in APS and the presence of systemic autoimmune disease does not worsen the clinical course of thrombosis in APS. The aim of this study is to draw a parallel between the intensity of inflammatory and coagulation responses in thrombotic primary APS (t-PAPS), compared with thrombotic secondary APS (t-SAPS), spontaneous VTE-non aPL and healthy controls. Patients were consecutively selected in the outpatient unit of the Hematology and Hemotherapy Center at the University of Campinas. Clinical data were collected in medical records and interviews with the participants. The markers of inflammation: interleukin (IL)-6, IL-8, TNF-α were measured by commercial ELISA, and high-sensitive hs-CRP by BN ProSpec® Kit. The markers of hemostasis: soluble tissue factor (sTF), von Willebrand factor (vWF) and a desintegrin and metalloprotease thrombospondin motifs (ADAMTS)-13 were measured by commercial ELISA. One hundred and seventy-three patients were included, 71 had t-PAPS, 44 had t-SAPS and 58 had spontaneous VTE-non aPL; 143 patients were women, 57 were men, the median age of patients were 42 years (IQ 29-52). One hundred twenty one controls, without personal history of thrombosis, were included; 88 were women, 33 were men, their median age was 42 years old (IQ 30- 52). Serum levels of the inflammatory markers TNF-α, CRP and IL-6 were higher in the three groups of thrombotic disease (VTE-non aPL, t-PAPS and t-SAPS) compared to controls. IL-8 levels were increased only in patients with t-SAPS, compared to controls. The relative risk (RR) for elevated TNF-α values were 11.9 for VTE, 4.4 for t-PAPS and 6.0 for t-SAPS (p <0.001). RR for increased values of CRP were 1.9 for VTE, 3.5 for t-PAPS and 3.8 t-SAPS (p <0.05). RR for elevated IL-6 levels were 5.8 for VTE, 3.4 for t-PAPS and 4.1 for t-SAPS (p <0.001). Among the coagulation markers, the imbalance between VWF and ADAMTS13 was observed in patients, compared to controls, but levels of VWF and ADAMTS13 activity were similar among the three groups of patients. Compared to controls, higher levels of VWF were equally found in patients with VTE (RR = 1.015; 95% CI = 1.008-1.023), t-PAPS (RR= 1.008; 95% CI= 1.002-1.015) and t-SAPS (RR= 1.010; 95% CI= 1.003-1.018), whereas lower levels of ADAMTS-13 activity were detected in VTE (RR = 0.94; 95% CI = 0.92-0.97 and t-SAPS (RR = 0.98; 95% CI= 0.97-0.99). Patients with t-PAPS and t-SAPS presented higher levels of sTF, compared to controls and VTE (RR = 1.008; 95% CI = 1004-1012 and RR= 1.011; 95% CI= 1.007-1.015, respectively). sTF values in patients with VTE were similar to controls. The adjustment for confounders (age, sex, BMI and comorbidities such as hypertension, dyslipidemia and diabetes) did not influence the estimated relative risks. Among patients with APS, levels of sTF correlated weakly with the levels of TNF-α (r=0.308, P=0.001) and IL-6 (r=0.315, P=0.001). Other inflammatory and coagulation markers did not present any statistical correlation. In conclusion, we observed that t-PAPS patients have an exacerbated inflammatory response when compared to controls, but the level of inflammation is similar to that observed in patients with spontaneous VTE-non aPL and t-SAPS. Despite the similar levels of inflammation, the procoagulant profile in t-PAPS, detected by sTF, was higher than in non-immune thrombosis. The results suggest that inflammation in t-PAPS may not be distinct from that observed in other non-immune thrombotic disorders, whereas the exacerbation of procoagulant stimulus seems to be more evident in t-PAPS than in non-immune VTE. Furthermore, we postulate that risk factors beyond inflammation may be related to the hypercoagulability detected in t-PAPS. DisclosuresNo relevant conflicts of interest to declare.

Comparative assessment of the prevalence of periodontal disease in subjects with and without systemic autoimmune diseases: A case-control study.

Background:Immune mechanism shares a common pathway both for systemic autoimmune diseases and periodontal diseases. Scientific exploration of literature revealed limited studies on the association between systemic autoimmune diseases and periodontal diseases in India.Aim:The aim of the study is to find whether the presence of systemic autoimmune diseases in an individual is a risk factor for the development of periodontal disease.Settings and Design:This was a hospital-based case–control study.Materials and Methods:A sample of 253 patients with systemic autoimmune diseases, attending the Rheumatology Department of Government General Hospital, Chennai-3, and 262 patients without systemic autoimmune diseases, attending the outpatient department of the Tamil Nadu Government Dental College and Hospital, Chennai-3, constituted the case and control groups, respectively. Age, gender, and oral hygiene status matching was done. Oral hygiene status was assessed using oral hygiene index (OHI) and periodontal status was assessed using community periodontal index (CPI) and loss of attachment (LOA) index.Statistical Analysis:Statistical analysis was done using SPSS version 15 (SPSS Inc, 2006, Chicago).Results:Results showed 99.2% and 73.9% prevalence of gingivitis and periodontitis, respectively, in the case group as compared to 85.5% and 14.9%, respectively, in the control group. There is no linear relationship between OHI scores and prevalence of periodontitis (CPI and LOA scores) in the case group. Patients suffering from systemic autoimmune diseases showed more prevalence of periodontal diseases irrespective of oral hygiene scores.Conclusion:It is postulated that the presence of systemic autoimmune diseases may pose a risk for the development of periodontal diseases.

Sequence analysis of TMEM173 exon 5 in patients with systemic autoimmune diseases

Background: Overactivation of the interferon pathways has been demonstrated in patients suffering from different systemic autoimmune diseases (SADs). Genetic associations have been described for many genes involved in these pathways. Gain-of-function mutations in the TMEM173 gene have recently been reported in patients with autoinflammatory diseases that share some clinical features with SADs. Methods: We aimed at detecting the reported three mutations of transmembrane protein 173 (TMEM173) exon 5 in 100 patients suffering from: systemic lupus erythematosus (SLE) (n = 22), primary antiphospholipid syndrome (PAPS) (n = 20), systemic sclerosis (SSc) (n = 20), dermatomyositis (DM) (n = 20), and vasculitis (n = 18). Samples from 19 healthy controls were also included. Sequence analyses were performed from the derived TMEM173 exon 5 PCR fragment amplified from DNA obtained from whole blood. Results: Neither mutations nor single nucleotide polymorphisms (SNPs) in the exon 5 of the TMEM173 gene were detected. Just the rs7380272 SNP, located in the intronic region upstream exon 5, was detected in some patients and controls. The allele frequency of this SNP, though, was not statistically different between the patients groups and the control group. Conclusions: Our study demonstrates the lack of association between the presence of SADs and mutations in exon 5 of the TMEM173 gene. SADs are complex multifactorial diseases in which not just one but probably many different genetic alterations may coexist. Although we cannot rule out the possibility that other variations may exist in other regions of this gene, we think that studies must be directed towards the analysis of other genes which, as TMEM173, also code for nucleic acid sensors that activate the nucleic-acid induced type I IFN pathway.

Comparison of Clinical Manifestations between Patients with Ocular Myasthenia Gravis and Generalized Myasthenia Gravis

PurposeTo compare the clinical manifestations between patients with ocular myasthenia gravis and those with generalized myasthenia gravis (MG).MethodsThe medical records of 71 patients diagnosed with MG between January 1995 and December 2007 were reviewed. Demographics, sensitivities of diagnostic methods, the presence of systemic autoimmune diseases, ophthalmic complications caused by MG, and treatments were evaluated and compared.ResultsFourteen patients (20%) were diagnosed with ocular MG and 57 patients (80%) with generalized MG. Sensitivities of anti-acetylcholine receptor antibody and repetitive nerve stimulation tests were significantly higher in the generalized MG group (84%, 89%) compared to those in the ocular MG group (50%, 54%) (p = 0.011, p = 0.008). The sensitivity of the neostigmine test was the highest in both groups (98% of generalized MG, 79% of ocular MG), and the difference between the two groups was borderline significant (p = 0.058). The most common symptoms were ptosis and diplopia, and both groups presented with pain, blurred vision, and tearing. Systemic autoimmune disease was more prominent in the generalized MG group (21%) than in the ocular MG group (14%), and steroid therapy was used more frequently in the generalized MG group (82%) than in the ocular MG group (57%). Ophthalmic complications associated with long-term steroid treatment were more profound in the generalized MG (30%) compared to those of the ocular MG (21%).ConclusionsThe generalized MG group was associated with higher sensitivities to diagnostic tests, more systemic steroid use, higher ophthalmic complications caused by systemic autoimmune disease, and long-term steroid treatment compared to those of the ocular MG group.

Autoimmunity and filariasis. Autoantibodies against cytoplasmic cellular proteins in sera of patients with onchocerciasis.

Onchocerciasis or "river blindness" is a vector-borne tropical disease resulting from infection with the filarial nematode Onchocerca volvulus. Disease manifestations include dermatitis, rheumatic complaints, and blindness. Recent findings have suggested an autoimmune etiology for the occurrence of chorioretinopathy, a disease of the eye which together with sclerosing keratoconjunctivitis is responsible for approximately 400,000 onchocerciasis-related cases of blindness. The identification of onchocerciasis as an important cause of tropical rheumatism prompted us to evaluate serologically the presence of systemic autoimmune disease in onchocerciasis patients and local controls from a hyperendemic area in Sierra Leone. In both groups there was a marked autoimmune response against cytoplasmic non-RNA-associated proteins consisting of autoantibodies against five major Ag with respective m.w. of 35, 51, 64, 83, and 110 kDa. These five proteins are novel autoantigens that could be distinguished from calreticulin, the human homologue of the onchocercal Ag RAL-1, and known autoantigens such as the 50-kDa La/SS-B or 52- and 60-kDa Ro/SS-A proteins by immunoblotting and ELISA assays. Furthermore, autoantibody reactivity against calreticulin was significantly higher in O. volvulus-infected individuals than in endemic controls. Autoantibody reactivity against the five major autoantigens, anti-calreticulin reactivity, and antibody reactivity against the 65-kDa arthritis-associated mycobacterial heat shock protein were intercorrelated as parts of an onchocerciasis-associated autoimmune response. The implication of autoimmunity in the disease pathogenesis of onchocerciasis could have important consequences for future research on therapeutical regimens, pathogenetic mechanisms, and serological diagnosis of onchocerciasis.