Current mechanistic insights into the role of infection in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by inflammation and abnormal production of autoantibody, but the mechanisms of the aberrant immune responses are currently unknown. Recently, growing evidence has suggested that infection plays a pivotal role in SLE. Here, we investigate the role of infectious agents (e.g., Epstein-Barr virus, parvovirus B19, human T-lymphotropic virus type 1, human immunodeficiency virus type 1, and endogenous retroviruses) in the pathogenesis of SLE. More importantly, we explore the known mechanisms underlying the involvement of infectious agents in the pathogenesis of SLE, including molecular mimicry, epitope spreading, superantigen production, bystander activation, persistent viral infection, altered apoptosis, clearance deficiency, and epigenetic alterations (e.g., DNA methylation and microRNAs). However, some infectious agents (e.g., malaria parasites, hepatitis B virus, Toxoplasma gondii, and Helicobacter pylori) may exert protective effects on SLE. Therefore, the relationship between infection and SLE is multifaceted and multidirectional, including causative and/or protective associations, which warrant further investigation in the future.

Diminished IL-17A levels may protect filarial-infected individuals from development of rheumatoid arthritis and systemic lupus erythematosus.

Nematode infections have been observed to inversely correlate with autoimmune disorders. Recently, we have shown the absence of filarial infection in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) who live in filarial-endemic areas. The mechanism(s) by which filarial-infected individuals are protected against the development of RA or SLE are unknown. In mice CIA, an experimental model for RA, ES-62, an execratory product of rodent filarial nematode , has been shown to improve arthritis through suppression of the IL-17 pathway. A total of 160 individuals, 40 each of endemic normal, filarial-infected cases, SLE and RA patients, from filarial-endemic areas, were enrolled in the study. Plasma levels of IL17-A, IFN-α and TNF-α were quantified by enzyme-linked immunosorbent assay (ELISA). RA and SLE patients displayed significantly higher plasma IL-17A, IFN-α and TNF-α levels compared to endemic normal and infected individuals. Furthermore, IL-17A levels were significantly low in participants with filarial infection compared to endemic controls ( p < 0.05). Interestingly, plasma IL-17A levels correlated inversely with circulating filarial antigen (CFA) ( p = 0.004, Spearman r = -0.51). Filarial infection was associated with low plasma IL-17A levels, a mechanism by which it possibly protects individuals in filarial-endemic areas from the development of autoimmune disorders like RA and SLE.

Interstitial granulomatous dermatitis associated with systemic lupus erythematosus: case report and review of the literature.

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease of unknown etiology that most frequently involves the skin and the musculoskeletal system. In addition to the more common cutaneous manifestations, interstitial granulomatous dermatitis (IGD) may rarely occur in association with SLE or even be the first sign of the disease. We describe a 40-year-old man with SLE-associated IGD, and review all cases of SLE-associated IGD in the literature.

Toxocara canis infection: Unusual trigger of systemic lupus erythematosus.

Infection by Toxocara canis can cause systemic vasculitis. We report here a unique case of systemic lupus erythematosus (SLE) triggered by T. canis infection. An 8-year-old girl was treated with albendazole therapy for common toxocariasis, but she developed two weeks later, asthenia, fever, infiltrated maculopapular eruption of the face, peripheral vascular disease with necrosis of the fingers and inflammatory anemia with proteinuria. Anti-nuclear, anti-DNA and anti-Sm antibodies positivity, together with minimal change nephritis with mesangial exclusive IgM deposit on renal biopsy and clinical relapse after initially successful steroid therapy, led to the diagnosis of SLE. T. canis infection can trigger systemic lupus but must also be ruled out of the differential diagnosis given its association with autoimmunity.

Infection of Female BWF1 Lupus Mice with Malaria Parasite Attenuates B Cell Autoreactivity by Modulating the CXCL12/CXCR4 Axis and Its Downstream Signals PI3K/AKT, NFκB and ERK.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by abnormal autoreactivity in B cells. Lymphocytes and their soluble mediators contribute to the disease pathogenesis. We recently demonstrated that infecting lupus mice with malaria confers protection against lupus nephritis by attenuating oxidative stress in both liver and kidney tissues. In the current study, we further investigated B cell autoreactivity in female BWF1 lupus mice after infection with either live or gamma-irradiated malaria, using ELISA, flow cytometry and Western blot analysis. The lupus mice exhibited a significant elevation in plasma levels of IL-4, IL-6, IL-7, IL-12, IL-17, IFN-α, IFN-γ, TGF-ß, BAFF and APRIL and a marked elevation of IgG2a, IgG3 and ant-dsDNA autoantibodies compared with normal healthy mice. Infecting lupus mice with live but not gamma-irradiated malaria parasite partially and significantly restored the levels of the soluble mediators that contribute to the progression of lupus. Furthermore, the B cells of lupus mice exhibited an increased proliferative capacity; aberrant overexpression of the chemokine receptor CXCR4; and a marked elevation in responsiveness to their cognate ligand (CXCL12) via aberrant activation of the PI3K/AKT, NFκB and ERK signaling pathways. Interestingly, infecting lupus mice with live but not gamma-irradiated malaria parasite restored a normal proliferative capacity, surface expression of CXCR4 and B cell response to CXCL-12. Taken together, our data present interesting findings that clarify, for the first time, the molecular mechanisms of how infection of lupus mice with malaria parasite controls B cell autoreactivity and thus confers protection against lupus severity.

Lupus-prone mice fail to raise antigen-specific T cell responses to intracellular infection.

Systemic lupus erythematosus (SLE) is characterized by multiple cellular abnormalities culminating in the production of autoantibodies and immune complexes, resulting in tissue inflammation and organ damage. Besides active disease, the main cause of morbidity and mortality in SLE patients is infections, including those from opportunistic pathogens. To understand the failure of the immune system to fend off infections in systemic autoimmunity, we infected the lupus-prone murine strains B6.lpr and BXSB with the intracellular parasite Toxoplasma gondii and survival was monitored. Furthermore, mice were sacrificed days post infection and parasite burden and cellular immune responses such as cytokine production and cell activation were assessed. Mice from both strains succumbed to infection acutely and we observed greater susceptibility to infection in older mice. Increased parasite burden and a defective antigen-specific IFN-gamma response were observed in the lupus-prone mice. Furthermore, T cell:dendritic cell co-cultures established the presence of an intrinsic T cell defect responsible for the decreased antigen-specific response. An antigen-specific defect in IFN- gamma production prevents lupus-prone mice from clearing infection effectively. This study reveals the first cellular insight into the origin of increased susceptibility to infections in SLE disease and may guide therapeutic approaches.

Sun, sangria and sandflies: Leishmaniasis in an immunosuppressed patient returning from Spain.

Despite the global financial downturn, millions of people continue to travel abroad each year. Many travel with co-morbidities such as immunosuppression, placing them at greater risk of bacterial, viral and parasitic infections.(1) Leishmaniasis is one of the principal neglected tropical diseases.(2) Although it threatens 350 million people each year(3) it is not an infection that most General Physicians would associate with travel to Southern Europe. A case of visceral leishmaniasis is described in a lady with mild immunosuppression caused by systemic lupus erythematosus, following a holiday in Southern Spain, a destination not normally associated with this leishmaniasis.

Fulminant amoebic colitis mimicking intestinal vasculitis in a patient with systemic lupus erythematosus.

Colitis in patients with systemic lupus erythematosus (SLE) is quite rare. It can be caused by intestinal vasculitis, mesenteric vascular thrombosis, concomitant inflammatory bowel disease or infectious colitis. It is important to make an accurate and early diagnosis as the treatments for each condition differ and a delayed diagnosis can result in life-threatening complications. However, non-specific gastrointestinal symptoms make a timely diagnosis challenging. Amoebic colitis is a rare condition in patients with SLE. Here we present a case of fulminant amoebic colitis in a patient with SLE which was initially misdiagnosed as ischemic colitis due to intestinal vasculitis. Her colitis was complicated with multiple intestinal perforations, disseminated intravascular coagulation and acute respiratory distress syndrome; but in the end, the patient was successfully treated with metronidazole and paromomycin.

Autoimmune and inflammatory mechanisms of CNS damage.

Brain morphology and function are susceptible to various psysiological influences, including changes in the immune system. Inflammation and autoimmunity are two principal immunological responses that can compromise the function of multiple organs and tissues, including the central nervous system. The present article reviews clinical and experimental evidence pointing to structural brain damage induced by chronic autoimmune and/or inflammatory processes. Largely due to the vast complexity of neuroendocrine and immune systems, most of the principal pathogenic circuits are far from elucidated. In addition to summarizing the current knowledge, this article aims to highlight the importance of interdisciplinary research and combined efforts of physicians and scientists in revealing the intricate links between immunity and mental health.

[A wolf in sheep's clothing: atypical systemic lupus erythematosus (SLE) presenting as cardiovascular disease]. / Der Wolf im Schafspelz: atypischer systemischer Lupus erythematodes (SLE) mit führender kardiovaskulärer Symptomatik.

CASE REPORT: A 51-year-old woman diagnosed as having valvular cardiomyopathy since age 34 was admitted for an evaluation for a heart transplant because of progressive congestive heart failure. When antiphospholipid antibodies were detected, the diagnosis of a thus far undetected systemic lupus erythematosus (SLE) was confirmed, manifesting primarily by cardiac involvement and an antiphospholipid antibody syndrome. Despite an advanced stage of heart failure, the patient responded well to azathioprine. Nevertheless, the potential necessity of a heart transplant remained. Its atypical presentation impeded a timely diagnosis of SLE significantly, however, in retrospect the correct diagnosis would have been possible at an earlier time point. CONCLUSION: Though rare, SLE represents an important differential diagnosis in cases of severe valvular disease and cardiomyopathy, particularly in young women.

Leishmania in SLE mimicking an exacerbation.

Systemic lupus erythematosus is a protean disease which may present manifestations that resemble other diseases posing serious problems of differential diagnosis. Visceral leishmaniasis is a parasitic infection, endemic in 88 countries, whose hallmarks may mimic a lupus flare. Fever, pancytopenia, splenomegaly, hypergammaglobulinemia, production of autoantibodies and complement consumption are some of the overlapping features between the two diseases. Thus, extra attention must be paid to patients with lupus who present with the mentioned symptoms. Diagnosis of visceral leishmaniasis relies on the detection of leishmania antibodies, on the presence of amastigotes in bone marrow aspirates, biopsies and cultures of the parasite. Treatment is based on the use of i.v. liposomal amphotericin B. The missed recognition of a leishmania infection in a lupus patient may lead to death, since both the omission of a specific anti-parasite treatment and the increase of the immunosuppressive therapy, in the conviction of a lupus flare, accelerate a fatal outcome. In this paper we present a case of visceral leishmaniasis occurring in a lupus patient. The clinical and laboratory features that overlap in the two diseases and the current literature on the topic were discussed.

Acanthamoeba encephalitis in patient with systemic lupus, India.

We report a fatal case of encephalitis caused by Acanthamoeba in a 24-year-old woman from India with systemic lupus erythematosus. Diagnosis was made by identification of amebas in brain sections by immunofluorescence analysis and confirmed by demonstrating Acanthamoeba mitochondrial 16S rRNA gene DNA in brain tissue sections.

Infections in systemic lupus erythematosus and rheumatoid arthritis.

Patients with systemic lupus erythematosus have a higher infection rate than the general population. It is estimated that at least 50% of them will suffer a severe infectious episode during the course of the disease. Improvements in the control of the disease are discussed in this article.

Fatal amoebic colitis in a patient with SLE: a case report and review of the literature.

Colitis in systemic lupus erythematosus (SLE) poses a diagnostic challenge as clinical, radiological and laboratory findings are often non-specific. Fulminant amoebic colitis is a rare cause of death in SLE. Early diagnosis coupled with timely surgery can reduce the mortality. The demonstration of haematophagous trophozoites in the stool is diagnostic but insensitive. Early endoscopy with adequate specimen collection is an important part of the diagnosis. Serology is both sensitive and specific but can take up to 2-4 weeks for seroconversion making it less useful in a disease that takes a rapid downhill course if treated inappropriately. We report a fatal case of colitis in a patient with SLE due to invasive amoebiasis which was complicated by Salmonella bacteraemia, disseminated intravascular coagulation, acute oliguric renal failure and adult respiratory syndrome. We also reviewed the literature on the clinical features and diagnosis of fulminant amoebic colitis. Amoebic colitis, although rare, should be considered in the differential diagnosis of lupus patients with colitis.

Estrongyloidiasis sistemica grave observacion de 3 casos / Sistemic strongy lodiasis. Report of 3 cases

El siguiente trabajo es un resumen de tres casos de Strongiloidiasis sistemica, en pacientes con factores predisponentes y uso de corticoides (los tres casos), droga inmunosupresoras (1 caso). La evolucion fue torpida en un inicio, pero con diagnostico oportuno y tratamiento adecuado, concluyeron bien . Tambien reportamos el uso de Ivermectina (derivado semisintetico de lactona macrociclica) nombre comercial Ivomec (actualmente se uso contra la filariasis y la cisticercosis en humano), droga utilizada en el paciente No.3, que no respondio al tratamiento convencional y cuya mejoria fue evidente luego del uso de esta.

Scabies and systemic lupus erythematosus.

There is little information in the literature concerning scabies in patients with systemic lupus erythematosus. Scabies in our five patients appeared to be more severe than usual, and two of them developed crusted scabies, probably on an immunologic basis.

Circulating non-human microfilaria in a patient with systemic lupus erythematosus.

A 12-yr-old girl with systemic lupus erythematosus requiring steroid therapy was found to have a circulating microfilaria during an exacerbation of her illness. Morphologically, the microfilaria does not correspond precisely with any previously described species, though similarities exist between the patient's microfilaria and those of Dipetalonema reconditum of the dog and D. interstitium of the grey squirrel. The organism reported here is probably an undescribed species from a wild mammal. Although the association may be merely coincidental, this case suggests that compromised immunity might have led to this unusual infection with a non-human filaria.