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PubMed2003

[Celiac disease and autoimmune diseases or systemic disease. Six cases and a review of the literature].

BACKGROUND: Celiac disease is an autoimmune disorder which may be associated with another autoimmune or systemic disease. OBJECTIVE: To determine the links between autoimmune diseases and celiac disease. PATIENTS AND METHODS: Among 31 patients with a celiac disease, we selected those who had another autoimmune or systemic disease. RESULTS: We report 6 patients with such disease association: 3 with autoimmune thyroiditis including one also with Grave's disease, 2 with systemic lupus erythematosus including one also with insulin-dependent diabetes mellitus, and 1 with temporal arteritis. CONCLUSION: The link between celiac disease and autoimmune thyroiditis or insulin-dependent diabetes mellitus seems to be real but many discrepancies are observed for the other autoimmune diseases. After a literature review, we suggest a summary of effective associations between celiac disease and autoimmune or systemic diseases.

Adolescent↗

PubMed2003

Consequences of autoimmune thyroiditis before, during and after pregnancy.

Autoimmune thyroiditis has important consequences for fertility, the occurrence of pregnancy complications, pregnancy outcome. Moreover autoimmune thyroiditis can aggravate during the postpartum period. Finally, the sequelae of autoimmune thyroiditis might have important consequences for the offspring. Several studies have shown an association between thyroid autoimmunity in earlyas opposed to beforepregnancy and subsequent "incidental" miscarriage. With respect to habitual abortion available data are more conflicting perhaps mild degrees of thyroid insufficiency - not detectable by routine thyroid testing - and not thyroid autoimmunity per se is causal in the association between the presence of thyroid antibodies and recurrent abortion. Autoimmune hypo- and hyperfunction during pregnancy are both related to obstetrical complications. It is important to note that treatment can - at least in part - reduce this excess risk associated with untreated hypo- or hyperthyroidism. Considering pregnancy outcome there are now data providing evidence that not only overt but also relatively mild and hitherto unrecognized states of thyroid failure are associated with persistent and significant impairment in neuropsychological performance of the offspring. Postpartum thyroiditis is clearly associated with the presence of TPO antibodies (i.e. autoimmune thyroiditis). Autoimmune thyroiditis is thus clearly associated with clinically relevant events, occurring before, during and after pregnancy. Screening should be considered; however further research is urgently needed.

Abortion, Spontaneous↗

PubMed2004

Triple association between hepatitis C virus infection, systemic autoimmune diseases, and B cell lymphoma.

OBJECTIVE: To analyze the clinical characteristics of patients from a Department of Autoimmune Diseases presenting chronic hepatitis C virus (HCV) infection, systemic autoimmune disease, and B cell lymphoma. METHODS: We analyzed the records of 100 consecutive patients with systemic autoimmune diseases and associated HCV infection seen in our department between 1994 and 2000. We retrospectively investigated the development of B cell malignancies after the diagnosis of HCV related autoimmune disease. RESULTS: Six patients with HCV related systemic autoimmune disease presented B cell non-Hodgkin's lymphoma (NHL). These patients fulfilled the diagnostic criteria for Sjögren's syndrome (n = 4) and polyarteritis nodosa (PAN; n = 2). Four patients were female and 2 male, with a mean age at lymphoma diagnosis of 62 years (range 45-78). The main immunologic markers were hypocomplementemia in all patients and cryoglobulinemia in 5 (83%). Primary extranodal localization of lymphoma was observed in 3 (50%) patients: prostate (n = 1), liver and ovary (n = 1), and ocular annexa (n = 1). Clinically, NHL was classified as indolent lymphoma in 3 patients and aggressive lymphoma in 3. NHL histologic types were diffuse large cell lymphoma (n = 4), extranodal marginal zone B cell lymphoma (n = 1), MALT lymphoma (n = 1), and lymphoplasmacytic lymphoma (n = 1). CONCLUSION: We describe 6 patients with a triple association of HCV infection, systemic autoimmune disease, and NHL. Characteristics of these patients included a high prevalence of cryoglobulinemia (that clearly contributes to fulfillment of diagnostic criteria for PAN) and an elevated frequency of primary extranodal involvement. We recommend careful evaluation of patients with B cell NHL to detect silent autoimmune or chronic viral diseases. This triple association reinforces the suspected links between autoimmunity, infection, and cancer.

Adult↗

PubMed2006

[Autoimmune thyropathies in diabetics].

Autoimmune thyropathies are frequent in patients with type 1 diabetes mellitus. Some recently published papers confirm similarly high prevalence of autoimmune thyropathies also in patients with type 2 diabetes mellitus. Chronic autoimmune thyroiditis is the most frequent form of autoimmune thyropathies. Authors examined 79 accidentally selected diabetics (38 women and 41 men, x = 55.4 +/- 2.8). Diabetic patients were divided into three groups. 20 patients with type 1 diabetes mellitus - classical form were the first group, 12 patients with LADA were the second group and 47 patients with type 2 diabetes mellitus constituted the third group. Authors diagnosed chronic autoimmune thyroiditis in 8 (40 %) patients in the group of patients with type 1 diabetes mellitus, in 6 (50%) in the group of patients with LADA and in 20 (43%) of patients with type 2 diabetes mellitus. They didn't find out statistically more frequent prevalence of chronic autoimmune thyroiditis in all groups of patients with diabetes (patients with type 1 diabetes mellitus, patients with LADA, patients with type 2 diabetes mellitus) in comparison with control group of non-diabetic subjects. They found out statistically significant more frequent prevalence of chronic autoimmune thyroiditis in diabetics of woman gender and in diabetics with positive family history of thyropathies. Results of paper confirm recommendation of examining once or twice a year autoantibodies against thyroid gland and level of thyrotropin (TSH) with the aim of early finding of laboratory manifestation of thyroidal autoimmunity or developing functional disorder.

Chronic Disease↗

PubMed2006

[The role of liver biopsy in the diagnosis of autoimmune hepatitis].

Autoimmune hepatitis is a progressive inflammatory hepatitis of unknown etiology. The diagnosis of autoimmune hepatitis is guided by the descriptive criteria and score system implemented by the International Autoimmune Hepatitis Group in 1994. In addition to clinical and laboratory data and the presence of autoantibodies, liver biopsy plays an important role in the diagnostic regimen. Previous studies have emphasized that the histological picture of autoimmune hepatitis was characteristic but not pathognomic for the disease, therefore diagnosis was based on the exclusion of other chronic liver diseases. The goal of this study is to summarize the experiences based on the examination of 93 liver biopsies from 87 patients suffering from autoimmune hepatitis in the Department of Pathology St. László Hospital, Budapest, during the period of 2000-2006. The morphological picture was evaluated based on the criteria of Histological Activity Index as well as other histological features. In addition it was compared to the usual histological characteristics of viral hepatitis, most importantly hepatitis C. The morphological changes examined first were the ones that constitute the diagnostic criteria of autoimmune hepatitis: the severity of portal inflammation and interface hepatitis, the cell composition of the inflammation, rosette formation of periportal hepatocytes, and the presence and extent of centrilobular and bridging necrosis. Results indicated that in most cases the portal/periportal inflammation was very active and lead to the destruction of the original liver structure which was followed by regeneration process (periportal rosettes). Among the inflammatory cells, plasma cells were predominant. In the majority of the cases severe centrilobular and/or bridging necrosis was also present, which strongly elevated the index number, approaching the maximum value. In most patients, only mild fibrosis was observed and merely a handful had progressed to cirrhosis. In conclusion the morphological picture of autoimmune hepatitis is not only characteristic but also pathognomic for the disease. Of course, additional data on clinical and biochemical findings, circulating autoantibodies, and abnormal levels of serum globulins are also necessary for correct diagnosis of autoimmune hepatitis.

Adolescent↗

PubMed2006

Clinical and immunologic aspects of B chronic lymphocytic leukemia associated with autoimmune disorders.

BACKGROUND: Autoimmune disorders often develop during the course of B chronic lymphocytic leukemia. The source of the autoantibodies is still uncertain: either uncontrolled production of the malignant B cells or disturbances of the residual normal B and T cells involved in the immune system. OBJECTIVES: To evaluate immunologic parameters in B-CLL associated with autoimmune disorders. As a hypothesis we postulated that in those cases, the malignant B cells might disclose an activated phenotype pattern leading to the production of autoantibodies. METHODS: In the Registry of the Israel Study Group on CLL that includes 964 patients, we found 115 cases showing a single or a complex of autoimmune disorders. We evaluated the lymphocyte morphology, immunoglobulin G and beta-2-microglobulin serum levels and positivity of the CD38 and FMC7 markers, and compared these values with those of a matched CLL population without autoimmune disorder. RESULTS: The main autoimmune disorders encountered were autoimmune hemolytic anemia (55 patients), Evan's syndrome (n=7), Hashimoto's thyroiditis (n=15), vasculitis (n=5) and rheumatoid arthritis (n=4). We found atypical prolymphocytic morphology in 22%, high expression of the activation antigens CD38 and/or FMC7 in 30%, and high level of immunoglobulin G (> 1000 mg/dl) and beta-2-microglobulin in 57% and 78% respectively. When compared with a matched CLL population without an autoimmune disorder, these values were statistically significant. CONCLUSIONS: Our data, which show activated lymphocyte morphology, high levels of IgG and beta-2-microglobulin, and increased expression of CD38 and/or FMC7 in a significant number of cases, suggest that some degree of activation of B cells may lead to the occurrence of an autoimmune disorder in CLL.

ADP-ribosyl Cyclase 1↗

PubMed1991

Expansion of the population of double negative CD4-8- T alpha beta-cells in the liver is a common feature of autoimmune mice.

There have been several reports that double negative (DN) CD4-8- T alpha beta-cells might be responsible for the onset of autoimmune diseases in humans and mice. We previously revealed that such DN T alpha beta-cells are generated in the liver of autoimmune MRL-lpr/lpr mice. In the present study, we further characterize the histology of the liver in these mice by light and electron microscopic studies. An intensive accumulation of mononuclear cells in the liver was demonstrated and a significant proportion of these mononuclear lymphocytes was found to intimately interact with Kupffer cells or endothelial cells of the hepatic sinusoids. The majority of such lymphocytes were TcR+CD4-8-Pgp-1+ alpha beta-cells. Identification of DN T alpha beta-cells was then performed in various autoimmune model mice. Interestingly, all autoimmune mice tested (i.e., MRL-lpr/lpr, C3H/HeJ-gld/gld, BXSB, NOD, MRL(-)+/+ and NZB/W F1 mice), showed an increased proportion of DN T alpha beta-cells (greater than 11% among all MNC) in the liver when they became old and diseased. On the other hand, young and old normal mice and young autoimmune mice before the onset of disease did not have such a high proportion of DN T alpha beta-cells (less than 10%) in the liver. Among autoimmune mice, MRL-lpr/lpr and C3H/HeJ-gld/gld mice had lymphadenopathy, which consisted of DN T alpha beta-cells (greater than 25%), after the onset of disease. Autoimmune mice of the other strains had neither lymphadenopathy nor DN T alpha beta-cells in the periphery, even when they were diseased. These results suggest that the expansion of the DN T alpha beta-cell population in the liver is a common feature of autoimmune mice, irrespective of the information of lymphadenopathy.

Animals↗

PubMed1991

Chronic infections and autoimmunity.

The studies summarized in this chapter indicate that chronic bacterial, viral, and parasitic infections can serve as a trigger factor of autoimmune reactivity according to various mechanisms. The relationship between microbes and autoimmunity could be manifested by the presence of autoantibodies, autoimmune complexes, or T cells with autoactivity. The presence of autoimmune phenomena in chronic infections could be related to polyclonal B-cell activation, molecular mimicry between microbial and host antigens, altered self, abnormal expression of immunoregulatory molecules, and the anti-idiotypic network. In most cases, the appearance of self-reactivity in the sera of patients with chronic infections is not associated with clinical manifestations. These findings suggest that autoimmune disease is the result of a combination of factors including immunologic, genetic, hormonal, and environmental. Infectious agents have a role in the breakdown of tolerance and the appearance of autoreactivity. However, only patients with the proper immunogenetic and hormonal background may develop clinical manifestations of autoimmune disease. In spite of the extensive knowledge that has accumulated, the specific relationship between infections and autoimmunity is still obscure. Clearly, additional studies are required to clarify the relevance of microbes to the pathogenesis of autoimmune diseases.

Acquired Immunodeficiency Syndrome↗

PubMed1990

Aberrant regulation of IL-1 expression in macrophages from young autoimmune-prone mice.

IL-1 is a multifunctional, immunoregulatory polypeptide produced by many cell types. Because activated macrophages are a major source of IL-1 and have also been implicated in the pathogenesis of autoimmune disease, we investigated the regulation of IL-1 expression in several autoimmune-prone strains of mice. Peritoneal macrophages derived from the autoimmune-prone strains MRL/lpr, MRL/+, NZB, and NZB/W F1, as well as NZW, displayed transient expression of IL-1 in contrast to the stable expression characteristic of control normal strains including A. Thy, A/J, B10, B10.A, B10.D2, C57BL/6, BALB/c, and C3H/HeN. The down-regulation of IL-1 by macrophages from the autoimmune-prone mice was not attributable to inherently defective signal transduction because macrophages from both the normal and autoimmune-prone strains displayed substantial initial levels of cell-associated and secreted IL-1. However, during the first 2 to 3 days in culture, macrophages from autoimmune-prone mice became progressively refractory to both induction and maintenance of IL-1, a pattern that correlated with changes in the levels of IL-1 alpha and beta mRNA. The progressive reduction in IL-1 expression by macrophages from these autoimmune-prone strains was not due to a reduction in general metabolism or viability, because expression of cell surface antigens, including MHC class I and II Ag and LFA-1, was comparable to that of control macrophages. Because IL-1 plays a critical role in the homeostasis of a variety of cell lineages, defective expression, and maintenance of IL-1 (and perhaps other cytokines) by macrophages from the autoimmune-prone strains may contribute to the immune dysregulation that develops in these mice. Alternatively, cytokine dysregulation might not contribute directly to disease, but rather reflect a more basic defect related to specific signal transducing or gene regulatory pathways.

Animals↗

PubMed1987

Mercury-induced autoimmune glomerulonephritis: requirement for T-cells.

Mercury-induced autoimmunity in Brown-Norway rats has been shown previously to be due to polyclonal activation of B lymphocytes, requiring the presence of T lymphocytes. Autoimmunity in that strain is characterised by the appearance of an autoimmune glomerulonephritis, by the production of a host of autoantibodies, and by an increase in total serum IgE. In the present study, T-cell deprived rats were tested to assess the role of T cells in the appearance of autoimmune abnormalities in vivo. It will be shown that both BN rnu/rnu and BN 'B' rats, who have virtually no T cells, do not develop autoimmunity following HgCl2 injections. In contrast BN 'B' rats reconstituted with normal T cells, and BN rnu/+ rats, exhibit autoimmune manifestations, including autoimmune glomerulonephritis, quite similar to those observed in Brown-Norway rats. These data demonstrate that T cells are essential for mercury-induced autoimmunity to occur in Brown-Norway rats.

Animals↗

PubMedDate not supplied

[Clinico-radiological comparisons in autoimmune thyroiditis].

The author observed 293 patients suffering from autoimmune thyroiditis (Hasimoto's thyroiditis--in 236). Four symptom complexes of the disease were distinguished: typical chronic autoimmune thyroidits in euthyroidal condition, chronic autoimmune thyroiditis with thyrotoxicosis, chronic autoimmune thyroiditis with hypothyroidism, relapsing autoimmune thyroiditis. Radioindication and scanning of the thyroid gland with radioactive iodine-131 was conducted preoperatively in 74 patients and at various postoperative periods in 26 patients. Radioisotopic methods were of importance in the comprehensive clinical examination of patients suffering from autoimmune thyroiditis. By means of these methods diagnosis of autoimmune thyroiditis was confirmed in 6.7% of patients. All the patients with autoimmune thyroiditis were operated on. Resection of the peritracheal segments of the thyroid gland with the isthmus extirpation was performed. During the postoperative period the patients required prolonged dispensary observation and treatment with immunodepressors and thyroid hormones.

Adult↗

PubMed1976

Immunopathogenesis of autoimmune tubulointerstitial nephritis. I. Demonstration of differential susceptibility in strain II and strain XIII guinea pigs.

Autoimmune tubulointerstitial nephritis (TN) was induced in strain XIII and Hartley but not strain II guinea pigs after immunization with rabbit tubular basement membranes (TBM) in CFA. Strain XIII guinea pigs developed extensive autoimmune TN associated with high anti-TBM (aTBM) antibody titers and linear deposits of IgG along renal cortical TBM after immunization with 10 mug to 10 mg of TBM. In addition, autoimmune TN was passively transferred to strain XIII animals by the i.p. injection of aTBM sera obtained from actively immunized Hartley guinea pigs. In contrast, strain II guinea pigs did not develop autoimmune TN after active immunization (10 mug to 10 mg) with rabbit TBM in CFA, and only produced high aTBM antibody titers with the highest immunnizing antigen dose. At this dose (10 mg) the strain II animals demonstrated linear deposits of IgG along renal cortical TBM but did not develop autoimmune TN. Further, recipient strain II guines pigs did not develop autoimmune TN after passive transfer of aTBM antisera despite renal cortical tubular deposition of aTBM antibodies. Both inbred guinea pig strains produced antibodies reactive with rabbit and rat renal basement membranes. No evidence for differences in nephritogenic TBM antigens could be demonstrated betweed strain XIII and strain II TBM. These observations indicate that 1) genetic factor(s) influence the production of antibodies reactive to autologous TBM, 2) after the deposition of antibodies on the TBM, additional or related genetic factor(s) determine the full expression of this autoimmune renal disease, and 3) aTBM antibody deposition on renal TBM is not sufficient to elicit autoimmune TN.

Animals↗

PubMed1994

Induction of autoimmune disease in mice by germline alteration of the T cell receptor gene expression.

Germline expression of rearranged TCR alpha-chain transgenes with the Ig H chain enhancer reproducibly elicits T cell-mediated autoimmune disease in the thyroid gland, gastric mucosa, Langerhans islets, salivary gland, ovaries, and testes in selected strains of normal mice. Multiple organs are destroyed in a single transgenic mouse and the same organ in transgenic strains with different MHC background, suggesting the transgene expression can elicit self-reactive T cell clones having different Ag specificities and MHC restrictions. Construction of this autoimmune-inducing TCR alpha EH transgene does not require particular V alpha J alpha gene segments or Ag specificities. Moreover, the autoimmune disease can be adoptively transferred to syngeneic normal mice by T cells expressing endogenous TCR alpha-chains. Taken together, these results indicate that the TCR alpha EH transgene expression does not suppress endogenous alpha-chain gene rearrangement and may trigger the expansion/activation of various self-reactive T cells expressing endogenous TCR alpha- and beta-chains. Furthermore, it appears that the transgene-induced autoimmune T cells are not deleted in the normal thymus or rendered anergic upon contact with the normal target self Ag, but can be controlled by a T cell-dependent mechanism, since transfer of the transgenic bone marrow cells to histocompatible SCID mice produces the same autoimmune disease as in the donors, and the autoimmune development in the SCID mice is effectively prevented by co-transfer of syngeneic nontransgenic T cells. This novel autoimmune model produced by genetic manipulation of the T cell lineage, not the target self Ag or the environment of T cell differentiation/selection, should be useful for elucidating the immunologic and genetic basis of autoimmune disease.

Age Factors↗

PubMed1998

[Association of extrahepatic autoimmune diseases in primary biliary cirrhosis--clinical statistics and analyses of Japanese and non-Japanese cases].

Abnormality of humoral and cellular immune functions and the association of autoimmune diseases are frequently observed in primary biliary cirrhosis (PBC). The prevalence of autoimmune diseases was studied in 97 Japanese patients with PBC. Sjögren's syndrome was diagnosed in 33 percent of these patients, arthritis in 22 percent, scleroderma in 11 percent, CREST syndrome in 4 percent, Raynaud's phenomenon in 8 percent, autoimmune thyroiditis in 3 percent, respectively. Fifty-five percent of the patients had at least one autoimmune disease and 19 percent had two or more such disorders. In this study, the prevalence of associated autoimmune diseases was somewhat low compared to that of European and American studies. Geographical variations, however, might exist in the prevalence of autoimmune associations, and the frequent occurrence of coexisting autoimmune diseases suggests an autoimmune pathogenesis in PBC.

Adult↗

PubMed2002

Increased prevalence of familial autoimmunity in simplex and multiplex families with juvenile rheumatoid arthritis.

OBJECTIVE: To determine if the prevalence of autoimmunity among relatives of patients with juvenile rheumatoid arthritis (JRA) is greater than that among relatives of healthy volunteer control subjects. METHODS: Interviews were used to obtain histories of the following disorders among living first- and second-degree relatives of 110 patients and 45 controls: alopecia areata, ankylosing spondylitis, dermatomyositis, Graves' disease, Hashimoto thyroiditis, insulin-dependent diabetes mellitus, inflammatory bowel disease, iritis, JRA, multiple sclerosis, psoriasis, RA, systemic lupus erythematosus, and vitiligo. Chi-squares, odds ratios (ORs), and 95% confidence intervals (95% CIs) were calculated. Families of 23 JRA affected sibpairs were interviewed subsequently. RESULTS: There were no significant differences between patients and controls with regard to age, sex, ethnicity, or family size. Patients had 1,228 relatives and controls had 496 relatives. Of all the relatives of the patients, 155 had at least 1 autoimmune disorder, compared with 20 relatives of the controls (12.6% versus 4.0%; OR 3.4 [95% CI 2.1-5.7], P < 0.000001). The prevalence of autoimmunity was increased in first-degree and in second-degree relatives of patients (16.1% and 10.6%, respectively). The prevalence of Hashimoto thyroiditis was significantly higher in the relatives of patients (OR 3.5 [95% CI 1.6-7.9], P = 0.0008). The prevalences of other disorders were not significantly different. JRA affected sibpair families had an increased prevalence of autoimmunity (15.0%). A history of arthritis was found significantly more frequently in the JRA affected sibpair families, but not in the simplex families. CONCLUSION: These data demonstrate that the prevalence of autoimmunity is significantly higher among first- and second-degree relatives of JRA patients. This suggests that clinically different autoimmune phenotypes may share common susceptibility genes, which may act as risk factors for autoimmunity.

Alopecia Areata↗

PubMed2003

Comparison of cytokine levels in sera of patients with autoimmune endocrinopathies.

Autoimmune endocrinopathies can be divided according to the presence of organ specific autoantibodies and according to the clinical manifestations into isolated autoimmune endocrinopathies, autoimmune polyglandular syndromes (APS) and polyglandular activation of autoimmunity (PAA). Many factors take part in the development of the autoimmune disease: predominantly a genetic predisposition, environmental etiologic causes and dysregulation in the microenvironment of the target organ. Until now it is not completely clear, if manifestations of the clinical disease depend primarily upon external factors and the degree of regulation mechanism disorder (e.g. in Th1/Th2 regulation) or upon the different genetic predisposition. In this work we compared the levels of Th1 and Th2 lymphocyte cytokines in peripheral blood in three groups of patients: group A of 30 patients with autoimmune thyroiditis, group B of 25 patients with PAA, and group C of 10 patients with APS type II. From group of Th1 cytokines IL-2 and IFN-gamma were detected, whereas from group of Th2 cytokines IL-4 and IL-10 were determined by ELISA kit. We did not find any differences in the concentrations of IL-2, IFN-gamma, IL-4 and IL-10 among the groups of patients with autoimmune endocrinopathies.

Autoimmune Diseases↗

PubMed2003

Update on autoimmune polyendocrine syndromes (APS).

Autoimmune Polyendocrine Syndromes (APS) were initially defined as a multiple endocrine gland insufficiency associated to an autoimmune disease in a patient. Neufeld & Blizzard (1980) suggested a classification of APS, based on clinical criteria only, describing four main types. APS-1 is characterized by presence of chronic candidiasis, chronic hypoparathyroidism, Addison's disease. It is a very rare syndrome interesting young subjects correlating to different mutations of AIRE (AutoImmuneRegulator) gene on chromosome 21. APS-2 is characterized by presence of Addison's disease (always present), autoimmune thyroid diseases and/or type 1 diabetes mellitus. It is a rare syndrome interesting particularly adult females and associated to a genetic pattern of HLA DR3/DR4. Autoimmune thyroid diseases associated to other autoimmune diseases (excluding Addison's disease and/or hypoparathyroidism), are the main characteristics of APS-3. The different clinical combinations of autoimmune diseases not included in the previous groups are characteristics of APS-4. In this paper criteria for defining a disease as autoimmune are presented. Furthermore, the classification, epidemiology, pathogenesis, genetic, animal models, clinical features, laboratory's tests, imaging, therapy, recent progresses in understanding the APS and a detailed analysis of large group of our patients affected by different types of APS are proposed and discussed.

Addison Disease↗

PubMed2002

Spironolactone blocks glucocorticoid-mediated hearing preservation in autoimmune mice.

HYPOTHESIS: Although autoimmune sensorineural hearing loss can be effectively treated with corticosteroids, little is known about how these drugs affect cochlear function. MRL/MpJ-Faslpr autoimmune mice treated with a mineralocorticoid (aldosterone) have previously been shown to have hearing improvement equal to those treated with a glucocorticoid (prednisolone). This suggested that the restoration of hearing with steroids was the result of an effect on sodium transport rather than an antiinflammatory or immunosuppressive role. We hypothesized that corticosteroids reverse autoimmune hearing loss through the mineralocorticoid receptor and that blocking the mineralocorticoid receptor will prevent glucocorticoid effects. METHODS: Spironolactone, a mineralocorticoid receptor antagonist, was administered to MRL/MpJ-Faslpr autoimmune mice alone or in combination with corticosteroids. The four treatment groups were: spironolactone, spironolactone + aldosterone, spironolactone + prednisolone, and untreated water controls. Auditory brainstem response (ABR) thresholds were recorded before and during treatment (2, 3, and 4 mo) to measure the effect of steroids on hearing decline. RESULTS: Hearing in spironolactone and spironolactone + prednisolone mice showed progressive decline in hearing similar to water controls. The hearing was preserved in spironolactone + aldosterone mice, presumably as a result of the fact that aldosterone has a higher affinity for the mineralocorticoid receptor than spironolactone. Thus, aldosterone was able to maintain cochlear function with autoimmune disease progression, similar to previous reports of aldosterone treatment effects. CONCLUSIONS: Spironolactone effectively blocked prednisolone from improving hearing in MRL/MpJ-Faslpr autoimmune mice. This offers evidence that the inner ear mineralocorticoid receptor is the therapeutic target for corticosteroids used to treat autoimmune and sudden sensorineural hearing loss. Pharmacologic treatments that selectively target the mineralocorticoid receptor may provide greater clinical benefit with fewer systemic side effects than prednisone in patients with autoimmune sensorineural hearing loss.

Aldosterone↗