Premature ovarian insufficiency and autoimmune diseases

Premature ovarian insufficiency (POI) is a clinical syndrome defined by loss of ovarian activity before the age of 40 years and has a potentially devastating effect upon women's health, both physically and psychologically. An underlying autoimmune disease has been identified in approximately 20% of patients with POI, the most common of which are disorders of the thyroid and adrenal glands. Nevertheless, in the majority of cases, the etiology is unknown. The damage mechanism to the ovary is usually caused by antibodies, and autoimmune POI is usually characterized by cellular infiltration of the theca cells of growing follicles by various inflammatory cells. Yet, other various factors and proteins of unknown clinical significance are present.The major diagnostic tool for otherwise idiopathic POI is the presence of autoantibodies against various ovarian components that strongly support the option of autoimmune etiology of POI.Treatment of the underlying cause of POI is the main strategy, although immunosuppressive therapy should be considered in a selected population of well-defined autoimmune POI and, as in idiopathic POI, in whom the resumption of ovarian activity is possible.     

Coinfection by Talaromyces marneffei and Mycobacterium abscessus in a human immunodeficiency virus-negative patient with anti-interferon-γ autoantibody: a case report

Patients with anti-interferon (IFN)-γ autoantibodies have weakened immune defenses against intracellular pathogens. Because of its low incidence and non-specific symptoms, diagnosis of anti-IFN-γ autoantibody syndrome is difficult to establish during the early stages of infection. Here, we report a patient with high titers of serum anti-IFN-γ autoantibodies suffering from opportunistic infections. The patient presented with intermittent fever for 2 weeks. During his first hospitalization, he was diagnosed with Talaromyces marneffei pulmonary infection and successfully treated with antifungal therapy. However, multiple cervical lymph nodes subsequently became progressively enlarged. Mycobacterium abscessus infection was confirmed by positive cervical lymph node tissue cultures. High-titer serum anti-IFN-γ antibodies were also detected. Following anti-M. abscessus therapy, both his symptoms and lymph node lymphadenitis gradually improved. Anti-IFN-γ autoantibody syndrome should be considered in adult patients with severe opportunistic coinfections in the absence of other known risk factors.     

甲状腺功能及其相关疾病与女性生殖关系的研究进展

正常的甲状腺功能有利于维持女性生殖系统的稳定。临床上常见的甲状腺功能亢进、甲状腺功能减退及自身免疫性甲状腺疾病等,均干扰了女性正常的卵巢功能,并影响体内的性激素水平,从而引发女性月经紊乱、排卵异常、不孕,甚至是对自然妊娠和辅助生殖技术的妊娠结局均产生不良影响。因此,完善育龄期妇女甲状腺功能的筛查,并深入甲状腺功能与女性生殖功能关联的研究,具有重要的临床意义。     

Role of physical factors in the pathogenesis of bullous pemphigoid: Case report series and a comprehensive review of the published work

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease affecting mainly the elderly. The subtype of the disease induced by physical agents represents a rare and, therefore, insufficiently characterized form. In the present study, we aimed to contribute to a better understanding of the pathogenetic mechanisms involved in the onset of BP induced by different trigger factors. We have retrospectively analyzed nine cases of BP. All patients were characterized based on clinical, epidemiological and immunological parameters. For each case, the trigger factor involved was specified. In addition to our retrospective analysis, a comprehensive review of the 59 published cases was conducted, regarding the involvement of trigger factor in BP, and clinical, epidemiological and immunological data were collected. In the local study, conducted on nine patients diagnosed with BP, various trigger factors were identified: contrast substance injection, surgical procedure, mechanical trauma, insect bite, thermal burn, radiotherapy and ultraviolet exposure associated with pre‐existing psoriasis. The autoantibodies from all patients were shown to activate granulocytes and induce dermal–epidermal split. Different hypotheses regarding the pathogenetic mechanism involving the trigger factors have been discussed. In regard of the pathogenetic mechanism, we believe that the most reliable hypothesis is that BP patients already have low titers of anti‐basement membrane autoantibodies which activate the granulocytes. However, more studies are needed for a better understanding of the pathogenetic mechanism of the intervention of trigger factors.     

Cambridge Neuropsychological Test Automated Battery in assessment of cognitive parameters in patients with systemic lupus erythematosus in relation to autoantibody profile

Objectives

To relate the cognitive parameters of systemic lupus erythematosus (SLE) patients in remission to their profile of autoantibodies.

Material and methods

The study included 32 patients with SLE in remission, with mild disease activity as indicated by SELENA-SLEDAI < 6. For neuropsychological assessment, the Cambridge Neuropsychological Test Automated Battery (CANTAB) was applied, using motor screening (MOT), big little circle (BLC), paired associated learning (PAL), stockings of Cambridge (SOC), and graded naming tests (GNT). Detection of autoantibodies against dsDNA, nucleosome (aNuc), Sm, and anticardiolipin (aCL: IgG and IgM) was performed with immunoassays.

Results

The SLE patients demonstrated standard scores below norms, matched according to age and gender, in the following tests: GNT (–0.87 ±0.85), SOC PSMM (–0.47 ±0.97), PAL (–1.88 ±3.58), and BLC (–0.31 ±1.90). GNT scores under –0.5 were found significantly more frequently in SLE patients, seen in roughly 66% of test subjects. Values for PAL and mean subsequent thinking time of stockings of Cambridge (SOC MSTT) were found to be lower than –0.5 in approximately half of the patients. Mean error of motor screening (MOT ME) was found to negatively correlate with mean latency of motor screening (MOT ML) (r = –0.55). PAL significantly correlated with SOC MSTT (r = 0.38) and with GNT (r = 0.36). Anti-dsDNA antibody level correlated negatively with MOT ME (r = –0.46). Anti-Nuc antibodies correlated with MOT ML (r = 0.41) but negatively correlated with MOT ME (r = –0.58). The levels of anti-Sm, anti-CL IgM and IgG did not correlate significantly with the outcomes of CANTAB. The age of the patients correlated negatively with MOT ME (r = –0.36), positively with BLC (r = 0.53) and negatively with SOC MSTT (r = –0.43). The level of anti-Nuc antibodies correlated with anti-dsDNA level (r = 0.62) and of anti-CL IgM with anti-Sm (r = 0.39) and anti-CL IgG (r = 0.87).

Conclusions

CANTAB reveals a decrease in selected cognitive functions in patients with SLE. ACL IgG and anti-dsDNA antibodies indicated SLE patients prone to develop a decrease in cognitive functions.     

The role of stress in the mosaic of autoimmunity: An overlooked association

Stress is defined as the pscyophysiological reaction in which the steady state is disturbed or threatened. Stress is not always perceived as a negative response. Stress results when environmental demands exceed an individuals' adaptive capacities. Autoimmune diseases are heterogeneous group of chronic diseases which occur secondary to loss of self antigen tolerance. The etiopathogenesis of autoimmune disease is uncertain. Genetic factors as well as environmental factors appear to interplay, leading to a cascade of events resulting in disease onset. Stress has been postulated to play a role in disease onset in the genetically susceptible patients. During the stress response, catecholamines and glucocorticoids are released from locus coeruleus and adrenal gland. These biomolecules exert control over various immune cells in the innate and adaptive arms of the immune system, thereby altering the cytokine profile released. The increase of IL-4 promotes T-helper 2 (T_h2) cell differentiation, while the decrease in IL-12 and the increased IL-10 production reduce the number of T-helper 1 (T_h1) cells. The relationship between stress and autoimmune diseases is intricate. Stress has been shown to be associated with disease onset, and disease exacerbations in rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, Graves' disease as well as other autoimmune conditions. In certain conditions such as psoriasis, stress has been implicated in delaying lesion clearance upon the application of standard treatment regimes. Finally, psychological therapy and cognitive behavioral therapy aimed to reduce stress levels was shown to be effective in influencing better outcomes in many autoimmune diseases. The purpose of this paper is to closer inspect the clinical evidence regarding the role of stress on influencing the various aspects of disease entities.     

Anti‐nuclear antibodies in patients with breast cancer

To study the prevalence of anti‐nuclear antibodies (ANA) in breast cancer patients and its association with tumour characteristics. Ninety‐one patients with breast mass detected by image studies and assigned to conduct diagnostic biopsy and eventual surgical treatment were studied for demographical, tumour data and presence of ANA. Serum of positive ANA patients was screened for the extractable nuclear antigen (ENA) profile. As comparison, 91 healthy individuals matched for age and from the same geographical area were included. In this sample 72 of 91 (79·1%) had malignant lesions (83% ductal infiltrative carcinoma). ANA was positive in 44·4% of patients with malignant tumour and in 15·7% of those with benign lesions (malignant versus benign with P = 0·03). Controls had ANA positivity in 5·4%, and when compared with tumour samples showed P < 0·0001. The most common immunofluorescence pattern was a fine dense speckled pattern. In the ANA‐positive patients with malignant lesions, seven had positivity for ENA profile (three for anti‐RNP and anti‐Sm, one for just anti‐RNP, two for anti‐Ro and anti‐La e two for just anti‐La). It was not possible to associate ANA positivity with tumour histological characteristics or staging or with patient's age. A negative association of ANA with hormonal (oestrogen or oestrogen plus progesterone) receptor status was found (P = 0·01). In this sample, there was a high prevalence of ANA positivity in breast cancer patients with a negative association with the presence of hormonal receptors. More studies are needed to understand the real value of this finding.     

Both B‐1a and B‐1b cells exposed to Mycobacterium tuberculosis lipids differentiate into IgM antibody‐secreting cells

Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. The cellular immune response to mycobacteria has been characterized extensively, but the antibody response remains underexplored. The present study aimed to examine whether host or bacterial phospholipids induce secretion of IgM, and specifically anti‐phospholipid IgM, antibodies by B cells and to identify the responsible B‐cell subset. Here we show that peritoneal B cells responded to lipid antigens by secreting IgM antibodies. Specifically, stimulation with M. tuberculosis H37Rv total lipids resulted in significant induction of total and anti‐phosphatidylcholine IgM. Similarly, IgM antibody production increased significantly with stimulation by whole Mycobacterium bovis bacillus Calmette–Guérin. The B‐1 subset was the dominant source of IgM antibodies after exposure to cardiolipin. Both CD5⁺ B‐1a and CD5^? B‐1b cell subsets secreted total IgM antibodies after exposure to M. tuberculosis H37Rv total lipids in vitro. Overall, our results suggest that the poly‐reactive B‐1 cell repertoire contributes to non‐specific anti‐phospholipid IgM antibody secretion in response to M. tuberculosis lipids.