P.-Y. Jeandel

Unraveling the Hygiene Hypothesis of helminthes and autoimmunity: origins, pathophysiology, and clinical applications

BackgroundThe Hygiene Hypothesis (HH) attributes the dramatic increase in autoimmune and allergic diseases observed in recent decades in Western countries to the reduced exposure to diverse immunoregulatory infectious agents. This theory has since largely been supported by strong epidemiological and experimental evidence.DiscussionThe analysis of these data along with the evolution of the Western world’s microbiome enable us to obtain greater insight into microorganisms involved in the HH, as well as their regulatory mechanisms on the immune system. Helminthes and their derivatives were shown to have a protective role. Helminthes’ broad immunomodulatory properties have already begun to be exploited in clinical trials of autoimmune diseases, including inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, and type-1 diabetes.SummaryIn this review, we will dissect the microbial actors thought to be involved in the HH as well as their immunomodulatory mechanisms as emphasized by experimental studies, with a particular attention on parasites. Thereafter, we will review the early clinical trials using helminthes’ derivatives focusing on autoimmune diseases.

Treatment with rituximab in patients with polyneuropathy with anti-MAG antibodies.

We report on a series of six patients diagnosed as anti-MAG polyneuropathy treated with rituximab. Nine months after the infusion of rituximab, sensory deficiency considered through the INCAT sensory score was improved in 5 patients and functional disability quantified by the overall neuropathy limitation scale was improved in 3 patients. Titers of anti-MAG antibodies and of monoclonal IgM gammapathy decreased respectively by 43% and 31%. No serious adverse event was observed. We did not find any predictive factors statistically related with the response to treatment.

Treating prolactinoma can prevent autoimmune diseases.

Prolactin (PRL) is a pleiotropic hormone; in addition to a wide variety of endocrine effects, PRL also exhibits immunostimulating effects. Therefore, there is increasing evidence linking PRL with a large number of systemic and organ specific autoimmune diseases. Herein, we report the case of an adolescent girl diagnosed with multiple sclerosis (MS) occurring in the context of untreated prolactinoma evolving since childhood. This raises the exciting question of the involvement of PRL in the pathogenesis of MS. It is likely that early treatment of hyperprolactinemia in this case would have significantly reduced the risk of developing MS or even prevented its occurrence.

Visceral leishmaniasis due to Leishmania infantum with renal involvement in HIV-infected patients

BackgroundWe describe histological, clinical findings and outcomes of renal involvement during Leishmania infantum infection in four HIV-infected patients in South France and North Italy hospital settings.Cases presentationFour HIV-infected Caucasian patients (age 24-49) performed renal biopsy during episodes of visceral leishmaniasis. They presented severe immunosuppression, frequent relapses of visceral leishmaniasis during a follow-up period of several years and partial or complete recovery of renal function after anti-parasitic treatment. Main clinical presentations were nephrotic or nephritic syndrome and/or acute renal failure secondary to membranoproliferative type III glomerulonephritis or acute interstitial nephritis. Clinical outcome was poor, probably as a consequence of insufficient immuno-virological control of the HIV infection.ConclusionsOur findings suggest that the main histological findings in case of renal involvement due to Leishmania infantum infection in HIV-infected patients are type III MPGN and acute interstitial nephritis, with a histological specificity similar to that observed in canine leishmaniasis. Poor immune status in HIV-infected patients, altering the capacity for parasite clearance, and prolonged course of chronic active VL in this population may lead to the development of specific renal lesions.

Efficacy and safety of biologics in relapsing polychondritis: a French national multicentre study

Objectives To assess the efficacy and the safety of biologics in a cohort of patients with relapsing polychondritis (RP). Methods We conducted a French multicentre retrospective cohort study including patients treated with biologics for RP. Efficacy outcomes were clinical response (partial or complete) and complete response during the first 6 months of exposure, plus daily corticosteroid dose at 6 months. Other outcomes were adverse drug reactions (ADRs), persistence of biologics and factors associated with a response. Results This study included 41 patients exposed to 105 biologics (tumour-necrosis factor (TNF) inhibitors, n=60; tocilizumab, n=17; anakinra, n=15; rituximab, n=7; abatacept, n=6). Overall response rate during the first 6 months of exposure was 62.9%. Complete response rate was 19.0%. Reduced corticosteroid doses were highly variable among patients. ADRs were mostly infections (n=42). Reasons for biologic withdrawal (73.3%) were insufficient efficacy (34.3%; ranging from 23.5% for tocilizumab to 72.7% for etanercept), loss of efficacy (18.1%) and ADRs (20.9%; mostly for anakinra: 46.7%). Persistence was comparable among biologic classes. Among TNF inhibitors, the highest persistence was observed with adalimumab. Differences in clinical response rates were observed depending on biologics and organ involvement. There were trends towards a lower response rate in cases with associated myelodysplastic syndrome and for a higher response rate for nasal/auricular chondritis, sternal chondritis and concomitant exposure to non-biologic disease-modifying antirheumatic drugs. Conclusions This study describes the efficacy of biologics for refractory RP. However, the number of complete responses was low and there were concerns about the risk of ADRs, particularly infections.

Hereditary angioedema and lupus: A French retrospective study and literature review.

Hereditary angioedema (HAE) is a rare genetic disorder that is primarily caused by a defect in the C1 inhibitor (C1-INH). The recurrent symptoms are subcutaneous edema and abdominal pain. Laryngeal edema, which can also occur, is life threatening if it goes untreated. HAE can be associated with some inflammatory and autoimmune disorders, particularly lupus. The aim of this study was to describe cases of lupus among HAE patients in France and to perform a literature review of lupus and HAE studies. Case detection and data collection (a standardized form) were performed, thanks to the French Reference Center for Kinin-related angioedema. Data were collected from 6 patients with type 1 HAE and lupus in France; no cases of systemic lupus erythematosus were reported. In the literature review, 32 cases of lupus combined with HAE were identified, including 26 female patients. The median patient age at the time of first reported HAE symptoms and at diagnosis were 17.5 years (range, 9-41 years) and 19 years (range, 9-64 years), respectively for our 6 patients and 14 years (range, 3-30 years) and 17 years (range, 7-48 years), respectively, for the literature review. The clinical manifestations of HAE were mainly abdominal pain (83% in our patients vs 47% in the literature) and edema of the limbs (83% vs 38%). The C4 levels were low (for 100% of our cases vs 93% in the literature). Eighteen patients in the literature demonstrated HAE symptoms prior to the lupus onset vs 5 for our patients. The mean patient age at lupus onset was 20 years (range, 13-76 years) for our patients and 19.5 years (range, 1-78 years) in the literature, respectively. In the literature, 81% of the patients had skin manifestations, 25% had renal involvement and 28% received systemic steroids to treat lupus. Treatment with danazol did not modify the clinical expression of lupus. The association between lupus and HAE is a rare but not unanticipated event. Patients are often symptomatic for HAE before developing lupus. Lupus cases associated with HAE share some characteristics of lupus cases related to other complement deficiencies, such as the absence of severity and the predominance of cutaneous symptoms.

Introduction to the special issue on the 9th International Congress on Autoimmunity

It is a great pleasure to introduce this special issue of Immunologic Research on the 9th International Congress on Autoimmunity held in Nice, France, on March 26–30, 2014. This special edition highlights a broad spectrum of emerging issues in the field of autoimmune diseases, both through original studies, reviews and case reports. Nice area and most particularly Grasse (France) might be the sweetest smelling city in Europe, widely known as the perfume capital in the world. While a superior olfactory sense, like that of Jean Baptiste Grenouille, the antihero of Patrick Süskind’s novel Perfume, may lead to addiction and psychiatric diseases, some olfactory function has been found to be impaired in patients affected by variety of autoimmune diseases. Recently, several studies have reported olfactory disorders in various immune-mediated diseases [1] including systemic lupus erythematosus (SLE) [2]. In this issue, two articles evaluate for the first time olfactory function in patients with idiopathic inflammatory myopathies (IIM) [3], fibromyalgia (FM) and systemic sclerosis (SSc) [4]. Thus, Iaccarino et al. [3] performed a case–control study in 60 patients with IIM using the Sniffin’ Sticks test, based on threshold, discrimination and identification (TDI) of odors. TDI score was found to be significantly lower in IIM patients when compared to ageand sex-matched healthy control individuals. Similarly, Amital et al. [4] investigated olfactory function in 24 patients with FM compared to 20 SSc and age-matched healthy controls. They demonstrated that TDI score was significantly decreased in FM and SSc compared with controls, the sense of smell being more deeply altered in patients with FM. The mechanisms of smell system damage in patients with autoimmune diseases are still elusive and are though to result from a complex interplay between genetic, environmental and hormonal factors [1]. In both articles, the role of depression as a potential confounding factor is still unclear. Unfortunately, none of these studies explored potential pathophysiological processes. Whether olfactory function may parallel disease activity or outcome should also be explored. Many women report a heightened sense of smell during pregnancy. Accounts of these anecdotes have existed for over 100 years, but scientific evidence has been sparse and inconclusive. A recent review [5] examined the literature on olfactory perception during pregnancy, showing no support for a general decrease in olfactory thresholds. This special issue examined more conventional aspects of pregnancy in the context of autoimmunity. Two authors have questioned predictive factors of SLE flares as well as of obstetric and fetal complications during pregnancy [6, 7]. Despite considerable progress in the identification of pre-conception, per pregnancy and puerperium risk factors for lupus flare, summarized by Jara et al. [7], it appears that predictive factors in pregnancy have not been systematically and fully elucidated. However, by prospectively following 132 pregnancies in 96 SLE patients, Borella et al. [6] reported that the number of flares before conception best predicted the risk of lupus flares during pregnancy. Moreover, manifestations during flares were even best predicted by the same features occurred before conception, illustrating Thucydides’ quote ‘‘History eternally repeats itself.’’ E. Rosenthal (&) M. Versini P.-Y. Jeandel Department of Internal Medicine, Centre Hospitalier Universitaire de Nice, Université de Nice Sophia Antipolis, 06200 Nice, France e-mail: rosenthal.e@chu-nice.fr