Is Sjögren's syndrome a retroviral disease?

Circumstantial evidence suggests that retroviruses play a role in the pathogenesis of Sjögren's syndrome. Such evidence, derived from studies of patients with Sjögren's syndrome, includes the following: the presence of serum antibodies cross-reactive with retroviral Gag proteins; the occurrence of reverse transcriptase activity in salivary glands; the detection of retroviral antigens, retrovirus-like particles, or novel retroviral sequences in salivary glands; the occurrence of Sjögren's syndrome-like illnesses in patients having confirmed systematic infections with retroviruses such as human immunodeficiency virus-1 (HIV-1) and human T lymphotropic virus type 1; and the beneficial effect of anti-retroviral treatment on the occurrence of HIV-1-associated sicca syndrome. Additional evidence is provided by animal models

The liver in brucellosis

Background & Aims: Brucellosis involves the liver in varying ways, ranging from benign subclinical increases in serum aminotransferase levels to ominous chronic suppurative disease. Data on histopathology of the liver in brucellosis are scarce and contradictory. We sought to determine the liver histologic patterns present in a series of brucellosis patients and review the existing knowledge about liver involvement in this worldwide, prevalent zoonotic infection. Methods: Fourteen patients from 2 referral centers were retrospectively studied. They had brucellosis caused by Brucella melitensis and had undergone liver biopsy at the time of diagnosis. Results: All patients exhibited granuloma formation in the liver parenchyma and in the majority in portal spaces. Varying degrees of cellular infiltration of parenchymal tissue and portal spaces, giant cells in granulomas, parenchymal necroses, and Kupffer’s cell hyperplasia were also noted. No significant epidemiological or clinical correlations with liver involvement were exhibited. Thus, liver involvement was not increased in men vs women, young vs old patients, or complicated vs uncomplicated disease. Conclusions: The liver is involved in Brucella melitensis infection contrary to past beliefs. Different histologic patterns can be observed in liver involvement in brucellosis, the most common being granuloma formation. The pathogenetic role of brucellosis in development of liver fibrosis and cirrhosis remains limited and understudied

Pattern and distribution of myocardial fibrosis in systemic sclerosis - A delayed enhanced magnetic resonance imaging study

Objective. To assess the prevalence and pattern of myocardial fibrosis as detected by delayed enhanced magnetic resonance imaging (DE-MRI) in patients with systemic sclerosis (SSc), and to evaluate a possible association between myocardial fibrosis and cardiac arrhythmias. Methods. Forty-one patients with SSc underwent 24-hour Holter monitoring, Doppler echocardiography, and DE-MRI following gadolinium administration. Results. Technically acceptable DE-MRIs were obtained in 36 patients with SSc. Enhancement on DE-MRI, consistent with myocardial fibrosis, was observed in 24 of these patients (66%), and it was invariably midwall with a linear pattern, mostly involving basal and midcavity segments of the left ventricle. The volume of enhancement (total volume percentage index [TVPI]) did not differ between patients with diffuse SSc and those with limited SSc- (mean +/- SD 1.46 +/- 1.73% versus 1.44 +/- 1.77%; P = 0.98). Patients with a long duration ( >= 15 years) of Raynaud’s phenomenon had a greater number of enhancing segments (mean +/- SD 6.55 +/- 4.93 versus 2.96 +/- 3.46; P = 0.017) and a greater TVPI (mean +/- SD 2.44 +/- 1.97% versus 1.02 +/- 1.43%; P = 0.02) than those with a duration of Raynaud’s phenomenon <15 years. Nineteen patients with SSc (53%) had abnormal Holler study results. Compared with patients with normal Holter study results, those with abnormal results had a greater number of enhancing segments (mean SD 5.4 +/- 4.8 versus 2.5 +/- 2.9; P < 0.05) and a greater TVPI (mean +/- SD 2.1 +/- 1.9% versus 0.8 +/- 1.2%; P < 0.05). Conclusion. DE-MRI can identify myocardial fibrosis in a significant percentage of patients with SSc and may be a useful noninvasive tool for determining cardiac involvement

Scleroderma specific autoantibodies in rheumatoid arthritis and Sjögren's syndrome patients with interstitial lung disease: Prevalence and associations

Systemic sclerosis (SSc) has been classically linked to interstitial lung disease (ILD) development, often in association with specific SSc autoantibodies. In the present report, we aimed to estimate the prevalence of SSc autoantibodies in 60 seropositive RA and 41 primary SS patients complicated or not by ILD. SSc autoantibodies were determined in patients’ sera by a commercial immunoblot assay. RA ILD patients displayed higher frequency of SSc-specific antibodies at strong titers compared to RA-with no lung involvement (25% vs 3.1%, p = 0.01)[OR 95% CI:10.9 (1.2–94.5)], with no differences detected between primary SS groups. These data indicate that many seropositive RA ILD patients probably represent an overlap RA/SSc entity, requiring tailored diagnostic and therapeutic approach

+3179G/A Insulin-Like Growth Factor-1 Receptor Polymorphism: A Novel Susceptibility Contributor in Anti-Ro/SSA Positive Patients with Sjögren’s Syndrome: Potential Clinical and Pathogenetic Implications

Background: Alterations of the insulin-like growth factor (IGF) pathway along with genetic variations of the IGF1 receptor (IGF1R) gene have been linked to the development of systemic autoimmunity, possibly through apoptosis induction. This study aims to investigate whether genetic variations of the IGF1R contribute to Sjögren’s syndrome (SS) pathogenesis and explores potential functional implications. Methods: DNA extracted from whole peripheral blood derived from 277 primary SS patients, complicated or not by lymphoma, and 337 Healthy controls (HC) was genotyped for the rs2229765 IGF1R polymorphism using the RFLP-PCR assay. Gene expression of IGF1R and IGF1 isoforms, caspases 1, 4, and 5, and inflammasome components NLRP3, ASC, IL1β, IL18, IL33, IGFBP3, and IGFBP6 were quantitated by RT-PCR in total RNA extracted from minor salivary gland biopsies (MSGs) of 50 SS patients and 13 sicca controls (SCs). In addition, IGF1R immunohistochemical (IHC) expression was assessed in formalin-fixed, paraffin-embedded MSG tissue sections derived from 10 SS patients and 5 SCs. Results: The prevalence of the A/A genotype of the rs2229765 IGF1R polymorphism was significantly higher in the anti-Ro/SSA positive SS population compared to healthy controls (24.8% vs. 10.7%, p = 0.001). Moreover, IGF1Rs at both mRNA and protein levels were reduced in SS-derived MSGs compared to SCs and were negatively associated with caspase 1 transcripts. The latter were positively correlated with NLRP3, ASC, and IL1β at the salivary gland tissue level. IGF1R expression in peripheral blood was negatively correlated with ESR and IgG serum levels and positively correlated with urine-specific gravity values. Conclusions: The rs2229765 IGF1R variant confers increased susceptibility for seropositive primary SS. Dampened IGF1R mRNA and protein expression in salivary gland tissues could be related to increased apoptosis and subsequently to the activation of inflammasome pathways

+3179G/A Insulin-Like Growth Factor-1 Receptor Polymorphism: A Novel Susceptibility Contributor in Anti-Ro/SSA Positive Patients with Sjogren's Syndrome: Potential Clinical and Pathogenetic Implications

Background: Alterations of the insulin-like growth factor (IGF) pathway along with genetic variations of the IGF1 receptor (IGF1R) gene have been linked to the development of systemic autoimmunity, possibly through apoptosis induction. This study aims to investigate whether genetic variations of the IGF1R contribute to Sjogren’s syndrome (SS) pathogenesis and explores potential functional implications. Methods: DNA extracted from whole peripheral blood derived from 277 primary SS patients, complicated or not by lymphoma, and 337 Healthy controls (HC) was genotyped for the rs2229765 IGF1R polymorphism using the RFLP-PCR assay. Gene expression of IGF1R and IGF1 isoforms, caspases 1, 4, and 5, and inflammasome components NLRP3, ASC, IL1 beta, IL18, IL33, IGFBP3, and IGFBP6 were quantitated by RT-PCR in total RNA extracted from minor salivary gland biopsies (MSGs) of 50 SS patients and 13 sicca controls (SCs). In addition, IGF1R immunohistochemical (IHC) expression was assessed in formalin-fixed, paraffin-embedded MSG tissue sections derived from 10 SS patients and 5 SCs. Results: The prevalence of the A/A genotype of the rs2229765 IGF1R polymorphism was significantly higher in the anti-Ro/SSA positive SS population compared to healthy controls (24.8% vs. 10.7%, p = 0.001). Moreover, IGF1Rs at both mRNA and protein levels were reduced in SS-derived MSGs compared to SCs and were negatively associated with caspase 1 transcripts. The latter were positively correlated with NLRP3, ASC, and IL1 beta at the salivary gland tissue level. IGF1R expression in peripheral blood was negatively correlated with ESR and IgG serum levels and positively correlated with urine-specific gravity values. Conclusions: The rs2229765 IGF1R variant confers increased susceptibility for seropositive primary SS. Dampened IGF1R mRNA and protein expression in salivary gland tissues could be related to increased apoptosis and subsequently to the activation of inflammasome pathways