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Influence of diet on the induction of experimental autoimmune thyroid disease.

Immunization of CBA/J mice with thryoglobulin (Tg) emulsified in complete Freund's adjuvant induces experimental thyroiditis (EAT), a well-characterized model of Hashimoto's disease. Recent studies have suggested that dietary factors play a role in the modulation of the immune response and that diet can have a profound effect on the induction of autoimmune diseases. In this study, we examined the influence of diet on autoimmune thyroiditis in mice. EAT was induced in mice fed ad libitum one of the three diets, a standard maintenance chow (Agway H1000), Purina 5020 Breeding Chow, and Purina 5010 Autoclavable (unautoclaved) Diet. Tg-immunized mice fed the Agway 1000 diet were found to be resistant to the development of autoimmune thyroid disease, with only 4 out of 25 mice developing mild thyroiditis. In contrast, 16 out of 25 mice fed the Purina 5010 diet developed moderate to severe thyroiditis. Mice fed the 5020 diet were partly susceptible: 7 out of 25 developed a mild to moderate thyroiditis. Histologic examination of thyroid glands of diseased mice fed the 5010 and 5020 diets showed marked lymphocytic infiltration with destruction of follicles, compared with mice fed the Agway diet, the latter showing only mild infiltration with preservation of thyroid follicles. Titers of antibody to Tg did not differ among the groups, and there was no significant difference in the IgG isotype subclass usage. The results demonstrate that diet can markedly affect the severity of autoimmune disease in the EAT model. In contrast, diet has little effect on the humoral autoimmune response in this system. These results implicate diet as a factor in the severity of cell-mediated autoimmune destruction and suggest that dietary modification could decrease pathology in some forms of autoimmune disease.

Animal Feed↗

Women and autoimmune diseases.

Autoimmune diseases affect approximately 8% of the population, 78% of whom are women. The reasons for the high prevalence in women are unknown, but circumstantial evidence links autoimmune diseases with preceding infections. Animal models of autoimmune diseases have shown that infections can induce autoimmune disease. For example, coxsackievirus B3 (CB3) infection of susceptible mice results in inflammation of the heart (myocarditis) that resembles myocarditis in humans. The same disease can be induced by injecting mice with heart proteins mixed with adjuvant(s), which indicates that an active infection is not necessary for the development of autoimmune disease. We have found that CB3 triggers autoimmune disease in susceptible mice by stimulating elevated levels of proinflammatory cytokines from mast cells during the innate immune response. Sex hormones may further amplify this hyperimmune response to infection in susceptible persons, which leads to an increased prevalence of autoimmune diseases in women.

Animals↗

Anti-erythroblast autoimmunity in early myelodysplastic syndromes.

BACKGROUND AND OBJECTIVES: Autoimmune phenomena, mainly directed against red blood cells are described in myelodysplastic syndromes (MDS), particularly early MDS, i.e. refractory anemia (RA) and RA with ringed sideroblasts (RARS). Dysregulation of apoptosis and immunoregulatory cytokines are thought to play a role in the pathogenesis of MDS. DESIGN AND METHODS: This work was aimed to investigate anti-erythroid autoimmunity in unstimulated and mitogen-stimulated peripheral blood and bone marrow cultures of 26 patients with early MDS (RA and RARS), and to relate its presence with apoptotic markers and cytokine production. Bone marrow cytokine production in culture supernatants, and caspase-3 and nuclear factor-kappaB activity in cell extracts were tested by enzyme-linked immunosorbent assays. RESULTS: Fourteen of the 26 (53.8%) patients showed the presence of autoantibodies in bone marrow cultures, whereas none displayed a positive direct antiglobulin test in peripheral blood cultures. Incubation of culture supernatants from positive patients with autologous CD45- enriched-cell suspensions showed that the autoimmune reaction was directed against autologous erythroblasts. These patients had mild signs of hemolysis and increased numbers of erythroblasts, compared with negative patients. Patients with anti-erythroblast autoimmunity displayed higher caspase-3 activity and lower tumor necrosis factor-alpha and interleukin-4 production than did negative patients. INTERPRETATION AND CONCLUSIONS: Half of the patients with early MDS showed autoimmunity against erythroblasts. This evidence might support a more rationale use of steroid therapy in these patients. The lower levels of cytokines in patients with anti-erythroblast autoimmunity are consistent with the suggested hypothesis that the autoimmune phenomena observed in MDS are probably initiated and perpetuated through alterations of pro-inflammatory and/or immunoregulatory cytokine production.

Adult↗

Autoimmune diseases as stem cell disorders: normal stem cell transplant for their treatment (Review).

Using various animal models for autoimmune diseases, we have found that autoimmune diseases are stem cell disorders. The transplantation of normal hemopoietic stem cells (HSCs) can be used to treat autoimmune diseases, whereas the transplantation of abnormal HSCs from autoimmune-prone mice to normal mice leads to the induction of autoimmune diseases in recipients. To elucidate the differences between normal and abnormal HSCs, we have established a new method for purifying pluripotent-HSCs (P-HSCs), and have compared the qualitative differences. Although normal P-HSCs cannot proliferate under major histocompatibility complex (MHC)-incompatible microenvironments (stromal cells), abnormal P-HSCs can proliferate under such conditions. In addition, the proliferation of abnormal P-HSCs is much faster than that of normal P-HSCs. These findings indicate that abnormal P-HSCs are more resilient than normal P-HSCs. Therefore, we propose that allogeneic bone marrow transplantation (BMT) (not autologous BMT) should be applied to the treatment of autoimmune diseases. human data on BMT in autoimmune diseases is reviewed, and the conditions essential for successful BMT, including tolerance induction, are discussed.

Animals↗

Antigen-based immunotherapy drives the precocious development of autoimmunity.

During the development of type I diabetes mellitus in nonobese diabetic (NOD) mice, T cell autoimmunity gradually spreads among beta cell Ags. Little is known about how autoantigen-based immunotherapies affect this spreading hierarchy. We treated newborn NOD mice with different autoantigenic beta cell peptides (in adjuvant) and characterized their T cell responses at 4 wk of age, when autoimmunity is usually just beginning to arise to a few beta cell Ag determinants. Surprisingly, we found that regardless of whether an early, or late target determinant was administered, autoimmunity had already arisen to all tested beta cell autoantigen determinants, far in advance of when autoimmunity would have naturally arisen to these determinants. Thus, rather than limiting the loss of self-tolerance, immunotherapy caused the natural spreading hierarchy to be bypassed and autoreactivities to develop precociously. Evidently, young NOD mice have a broad array of beta cell-reactive T cells whose activation/expansion can occur rapidly after treatment with a single beta cell autoantigen. Notably, the precocious autoreactivities were Th2 type, with the exception that a burst of precocious Th1 responses was also induced to the injected autoantigen and there were always some Th1 responses to glutamic acid decarboxylase. Similarly treated type 1 diabetes mellitus-resistant mouse strains developed Th2 responses only to the injected Ag. Thus, autoantigen administration can induce a cascade of autoimmune responses in healthy (preautoimmune) mice that are merely genetically susceptible to spontaneous autoimmune disease. Such phenomena have not been observed in experimental autoimmune disease models and may have important clinical implications.

Amino Acid Sequence↗

Maternal autoantibody triggers de novo T cell-mediated neonatal autoimmune disease.

Although human maternal autoantibodies may transfer transient manifestation of autoimmune disease to their progeny, some neonatal autoimmune diseases can progress, leading to the loss of tissue structure and function. In this study we document that murine maternal autoantibody transmitted to progeny can trigger de novo neonatal pathogenic autoreactive T cell response and T cell-mediated organ-specific autoimmune disease. Autoantibody to a zona pellucida 3 (ZP3) epitope was found to induce autoimmune ovarian disease (AOD) and premature ovarian failure in neonatal, but not adult, mice. Neonatal AOD did not occur in T cell-deficient pups, and the ovarian pathology was transferable by CD4(+) T cells from diseased donors. Interestingly, neonatal AOD occurred only in pups exposed to ZP3 autoantibody from neonatal days 1-5, but not from day 7 or day 9. The disease susceptibility neonatal time window was not related to a propensity of neonatal ovaries to autoimmune inflammation, and it was not affected by infusion of functional adult CD4(+)CD25(+) T cells. However, resistance to neonatal AOD in 9-day-old mice was abrogated by CD4(+)CD25(+) T cell depletion. Finally, neonatal AOD was blocked by Ab to IgG-FcR, and interestingly, the disease was not elicited by autoantibody to a second, independent native ZP3 B cell epitope. Therefore, a new mechanism of neonatal autoimmunity is presented in which epitope-specific autoantibody stimulates de novo autoimmune pathogenic CD4(+) T cell response.

Administration, Oral↗

Myosin autoimmunity is not essential for cardiac inflammation in acute Chagas' disease.

Infection with the protozoan parasite Trypanosoma cruzi leads to acute myocarditis that is accompanied by autoimmunity to cardiac myosin in susceptible strains of mice. It has been difficult to determine the contribution of autoimmunity to tissue inflammation, because other inflammatory mechanisms, such as parasite-mediated myocytolysis and parasite-specific immunity, are coincident during active infection. To begin to investigate the contribution of myosin autoimmunity to myocarditis, we selectively inhibited myosin autoimmunity by restoring myosin tolerance via injection of myosin-coupled splenocytes. This tolerization regimen suppressed the strong myosin-specific delayed-type hypersensitivity (DTH) that normally develops in infected mice, although it did not affect myosin-specific Ab production. Suppression of myosin autoimmunity had no effect on myocarditis or cardiac parasitosis. In contrast, myosin tolerization completely abrogated myocarditis in mice immunized with purified myosin, which normally causes severe autoimmune myocarditis. In this case, myosin-specific DTH and Ab production were significantly reduced. We also examined the contribution of T. cruzi-specific immunity to inflammation by injection of T. cruzi-coupled splenocytes before infection. This treatment reduced T. cruzi DTH, although there was no effect on parasite-specific Ab production. Interestingly, cardiac inflammation was decreased, cardiac parasitosis was significantly increased, and mortality occurred earlier in the parasite-tolerized animals. These results indicate that myosin-specific autoimmunity, while a potentially important inflammatory mechanism in acute and chronic T. cruzi infection, is not essential for inflammation in acute disease. They also confirm previous studies showing that parasite-specific cell-mediated immunity is important for myocarditis and survival of T. cruzi infection.

Acute Disease↗

Infections and autoimmunity--good or bad?

The relationship between infections and autoimmunity is complex. Current evidence indicates that microbes can initiate, enhance, or, conversely, abrogate autoimmunity. In this paper, we will review experimental examples illustrating mechanisms involved in these three scenarios. Microbial infections can act as environmental triggers inducing or promoting autoimmunity resulting in clinical manifestations of autoimmune disease in genetically predisposed individuals. However, increasing evidence suggests the opposite outcome, which is the prevention or amelioration of autoimmune processes following microbial encounters. These latter observations support conceptually the "hygiene hypothesis," suggesting that cleaner living conditions will lead to enhanced incidence of autoimmune disorders, asthma, and allergies. Because proof of concept in humans is difficult to obtain, we will discuss relevant animal model data in context with likely or proven human associations. Knowledge of mechanisms that underlie either positive or negative effects of infections on autoimmunity will facilitate exploration of molecular details for prospective clinical studies in the future.

Animals↗

Pathogenic consequences in semen quality of an autoimmune response against the prostate gland: from animal models to human disease.

We have recently proposed an autoimmune etiology in approximately 35% of chronic nonbacterial prostatitis patients, the most frequent form of prostatitis observed, because they exhibit IFN-gamma-secreting lymphocytes specific to prostate Ags. Interestingly, this particular group of patients, but not the rest of chronic nonbacterial prostatitis patients, also presented striking abnormalities in their semen quality. In this work, we use an experimental animal model of autoimmune prostatitis on Wistar rats developed in our laboratory to investigate when, where, and how sperm cells from autoimmune prostatitis individuals are being damaged. As in patients, a marked reduction in sperm concentration, almost null sperm motility and viability, and an increased percentage of apoptotic spermatozoa were detected in samples from animals with the disease. Prostate-specific autoantibodies as well as elevated levels of NO, TNF-alpha, and IFN-gamma were also detected in their seminal plasma. In contrast, epididymal spermatozoa remain intact, indicating that sperm damage occurs at the moment of joining of prostate secretion to sperm cells during ejaculation. These results were further supported by experiments in which mixture of normal sperm cells with autoimmune seminal plasma were performed. We hypothesize that sperm damage in experimental autoimmune prostatitis can be the consequence of an inflammatory milieu, originally produced by an autoimmune response in the prostate; a diminished prostate functionality, evidenced by reduced levels of citric acid in semen or by both mechanisms simultaneously. Once more, we suggest that autoimmunity to prostate may have consequences on fertility.

Animals↗

[Systemic autoimmune disease in patients with uveitis].

OBJECTIVE: A descriptive study was conducted on patients with uveitis to determine the frequency of associated autoimmune systemic diseases. METHODS: 64 patients with uveitis were studied. The patients were not known to have an underlying autoimmune systemic disease prior to the diagnosis of uveitis. All patients had the following immunological tests performed: serum immunoglobulins, complement components, circulating immune complexes (CIC), antinuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA), anti-cardiolipin antibodies (ACA) and major histocompatibilty complex antigens. RESULTS: A relationship with a sub-clinical autoimmune systemic disorder could be presumed in eleven cases (17.2%). This was defined by positive autoantibodies (ANA, ANCA or ACA) in the presence of complement consumption, hyper-gammaglobulinemia or increased CIC without clinical criteria of a defined autoimmune disease. A definite association with systemic autoimmune disease was defined in four patients (6.25%). The observed autoimmune systemic diseases were Sjögren's syndrome (n=2, 3.13%), anti-phospholipid syndrome associated with lupus-like disease (n=1, 1.6%), and systemic vasculitis (n=1, 1.6%). Lupus-like disease (n=4, 6.25%) was also observed. CONCLUSION: In a significant proportion of patients with uveitis an autoimmune systemic disorder may be present and should be looked for.

Adult↗

Autoimmunity after alpha-interferon therapy for malignant carcinoid tumors.

OBJECTIVE: To determine the incidence of autoantibodies and autoimmune disease and their influence on therapeutic results during alpha-interferon treatment in patients with malignant midgut carcinoid tumors. DESIGN: Consecutive sample of patients. SETTING: University hospital. PATIENTS: One hundred thirty-five patients (70 women, 65 men; median age, 59 years) with biopsy-proven tumors, liver metastases, and no autoimmune disease. INTERVENTIONS: Leukocyte alpha-interferon (n = 88) or alpha-interferon 2b (n = 47) three times a week. MAIN OUTCOME MEASURES: Signs and symptoms of autoimmune disease or development of autoantibodies to thyroid antigens, nuclear antigens, or gastric parietal cells. Tumor responses were determined by reduced liver metastases or reduced urinary 5-hydroxyindole acetic acid excretion, or both. RESULTS: Twenty-five patients (19%) developed the following autoimmune disorders after a median of 9 months of therapy: thyroid disease (n = 18), systemic lupus erythematosus (n = 1), pernicious anemia (n = 4), and vasculitis (n = 2). Antibodies to microsomal thyroid antigen or thyroglobulin were detected in 16 patients before therapy and in another 11 patients during therapy. Antinuclear antibodies were detected in 16 patients before and in another 19 patients during therapy. Clinical thyroid disease developed in more than 60% of patients who had or developed thyroid antibodies but in only 7% of initially autoantibody-negative patients. Autoimmunity did not correlate with objective tumor response. CONCLUSION: Patients with malignant carcinoid tumors may develop autoimmune disease during alpha-interferon therapy, especially when autoantibodies are present. They should therefore be monitored for autoimmunity, which does not appear, however, to influence tumor responses.

Adult↗

Thyroid autoimmunity in children and adolescents with Type 1 diabetes mellitus.

Type 1 diabetic children and adolescents often present with autoimmune thyroid disorders. Two hundred and four diabetic patients, less than 20 years old, were studied in order to diagnose these diseases. The prevalence of thyroid autoimmune disorders was 17.6% and, of those, chronic autoimmune thyroiditis was the most frequent. Microsomal autoantibodies correlated more accurately with the presence of chronic autoimmune thyroiditis than thyroglobulin autoantibodies. The thyroid status of most of the patients with positive markers was euthyroidism (77%), but subclinical hypothyroidism (11%), overt hypothyroidism (3%), subclinical hyperthyroidism (3%) and overt hyperthyroidism (6%) were also present. Autoimmune thyroid disorders were the most prevalent immunological processes affecting diabetic patients. No significant associations of thyroid autoimmunity and other autoimmunological disorders, such as celiac disease or presence of other autoimmune antibodies, were found.

Adolescent↗

Cytotoxic effector function in HLA-associated autoimmune diseases.

BACKGROUND: The mechanisms by which cytotoxic-T-lymphocytes (CTLs) and natural killer (NK) cells recognize and kill target cells are the subject of intense research. Previous observations in patients with HLA-associated autoimmune diseases show a major impact of cell-mediated immunity as compared to antibody-mediated immunity. This study analyzes the possible co-operation of NK cells in the autoimmune process, comparing their increase to that of cytotoxic-T-lymphocytes. METHODS: This research examines the incidence of CD8+ T cells and NK cells increases in 1065 patients with various autoimmune diseases. Tissue typing for HLA antigens was carried out in all patients by conventional serologic methods. Lymphocyte subsets (CD4+, CD8+, CD3-HLA-DR+, NK cells, sIg+ B cells) were detected with monoclonal antibodies by a fluorescent cytometer. Results were statistically compared to normal control values by the Student's "t"-test. RESULTS: The analysis of results shows the incidence of CTLs and NK cell increases in patients with different autoimmune syndromes. In some diseases (uveitis, multiple sclerosis, and other neurological autoimmune disorders) raised frequencies of NK cell increase are most evident. These results suggest some possible relationships between CTLs and NK cells in the pathogenesis of the autoimmune process. CONCLUSIONS: The present results show that CTLs and NK cells are implicated in immune dysregulation, which characterizes the complex pathogenesis of autoimmune diseases.

Autoimmune Diseases↗

Autoimmune manifestations in patients with primary immunodeficiency.

Primary immunodeficiency comprises a heterogeneous group of disorders. Autoimmune and/or rheumatic manifestations are not uncommon in these patients. It may be the first and/or sole sign before the underlying disease is established. This study focuses on the children of primary immunodeficiency with autoimmune disease to survey the clinical and laboratory finding retrospectively. From January 1985 to June 1998, ten patients (M:F = 9:1) of primary immunodeficiency with at least one well defined autoimmune disease were identified. The underlying immunodeficiency included three with Bruton's disease, three with common variable immunodeficiency, one with hyper-IgM, one with primary CD4 T-cell deficiency and two with Wiskott-Aldrich syndrome. The autoimmune manifestations include arthritis in six, ulcerative colitis in one, and autoimmune hemolytic anemia in three children. The major treatment was steroid and non-steroid anti-inflammatory drug. Infection could be controlled with antibiotics and intravenous immunoglobulin in all save one. The morbidity among these patients included bronchiectasis with pulmonary hypertension in three, joint stiffness, short stature, and delayed puberty in two. In conclusion, autoimmune diseases are frequently seen in patients with primary immunodeficiency. It could be the first and/or sole sign of disease. The possibility of immunodeficiency should be kept in mind when evaluating patients with autoimmune diseases.

Autoimmune Diseases↗

[Autoimmune hepatitis in children].

UNLABELLED: Autoimmune hepatitis is a rare chronic disease of unknown aetiology with female predominance, circulating autoantibodies, hypergammaglobulinaemia, typical major human leukocyte antigen types (HLA A1/B8/DR3) and a good response to immunosuppressive therapy. It seems that the main features in autoimmune hepatitis are a primary or secondary defective suppressor-T-cell function. Recently, we are realizing the recommendations of the International Autoimmune Hepatitis Study Group, using a combination of clinical, biochemical and serological features. METHODS: Two hundred and twenty one patients with chronic liver disease were studied. In this study, 221 consecutive percutaneous liver biopsies were performed, with a Menghini needle, during a 5-year period. All children were under 18 years. RESULTS: We found 17 patients with autoimmune hepatitis (7.7%) among children with chronic liver disease. In summary, final diagnosis was established in 16 patients (94%). Using minimum required (main) parameters final diagnosis was established in 10 patients (59%). We found no significant differences between histologic parameters and response to therapy. Our patients with autoimmune hepatitis were predominantly females (3.25:1) with antibodies to smooth muscle (59%). The main histologic findings were bridging necrosis, rosetting of the liver cells and plasma cell infiltration (83%). In two cases we found granulomas and in one case centrilobular necrosis. DISCUSSION AND CONCLUSION: Over a period of 5 years, the diagnosis of autoimmune hepatitis was established in 17 children. This is similar to the findings published in other paediatric studies [7, 8]. Patients were predominantly females as in the most recent studies [10, 11, 13-15]. Our results regarding the validation of the scoring system showed that we found no significant differences between histologic parameters and response to therapy [16-18]. Histologic findings were not pathognomonic but suggestive of autoimmune hepatitis diagnosis [1, 4, 8, 15-18]. The remission rate induced by the initial therapy was 88%, but in 53% of cases the disease was reactivated [3, 4, 11, 14, 15].

Adolescent↗

Immunodeficiency and autoimmunity.

The following aspects of autoimmunity and immunodeficiency will be discussed: 1) Autoantibodies and autoimmunity and their relationships to human disease and particularly to the rheumatic diseases. 2) Relationships between human immunodeficiency diseases and autoimmunity including: a) autoimmune disease in patients with immunodeficiency; b) arthritis in patients with immunodeficiency; c) lupus-like illness in carriers of chronic granulomatous disease; d) occurrence of autoantibodies and autoimmunity in relatives of patients with immunodeficiency. 3) Immunodeficiency as a basis for human rheumatic or autoimmune diseases. The role of immunodeficiency in NZB mouse diseases and human SLE. 4) The role of viral infections in autoimmune disease.

Adult↗

Aortic aneurysm in patients with autoimmune diseases treated with corticosteroids.

BACKGROUND: Aortic aneurysm is a rare but life-threatening cardiovascular complication in patients with autoimmune disorders. The purpose of this study was to clarify the characteristic clinical features and the pathological mechanism of aneurysmal formation in those patients treated with corticosteroids. METHODS: Among 429 patients operated on for abdominal aortic aneurysm during the past 10 years, six patients with autoimmune diseases treated with corticosteroids (one with progressive systemic sclerosis, one with rheumatoid arthritis and four with systemic lupus erythematosus) were reviewed retrospectively. Their data were compared with those of 391 patients with atherosclerotic aneurysms with no autoimmune disorders. The resected aneurysmal walls of the six patients were also compared histopathologically with those of the last six consecutive patients in the control group. RESULTS: The average age of the patients with autoimmune disease was younger than that of the control group (53.8+/-16.6 vs 71.8+/-7.8 years; p<0.05). Patients with autoimmune disease had received long-term corticosteroid therapy for 15-32 years; mean 22.2+/-6.5 years. Pathological examination showed that the destructive change of the medial elastic lamina in the autoimmune disease group was wider than that in the controls. Most patients had no complications in the postoperative follow-up period (5.1+/-3.2 years), while one patient died of rupture of a dissecting aneurysm two years after operation. CONCLUSIONS: Prolonged corticosteroid treatment probably plays a major role in the disintegration of connective tissue of the media, possibly together with primary aortic wall involvement and/or vasculitic damage in patients with autoimmune disorders, which can result in aortic aneurysmal enlargement.

Adrenal Cortex Hormones↗

Immunoablation followed by autologous hematopoietic stem cell infusion for the treatment of severe autoimmune disease.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the tolerability and effectiveness of a non-myeloablative conditioning regimen followed by autologous hematopoietic stem cell infusion for the treatment of severe autoimmune diseases. DESIGN AND METHODS: From 1996 patients with severe autoimmune disease not responsive to conventional immunosuppressive treatment were selected. The patients' blood or marrow cells were harvested after incubation with vincristine and methylprednisolone. Two different immunoablative conditioning regimens were employed. The first used cyclophosphamide (2500 mg/m2 in one day) and antilymphocyte globulin (ALG) (15 vials/m2 in three days) and the second used fludarabine (300 mg/m2 in two courses of 5 days) plus ALG (25 vials/m2 in 5 days). RESULTS: Nineteen patients (14 female, 5 male) with severe autoimmune diseases were treated. Nine had a rheumatologic disorder (5 juvenile chronic arthritis, 1 rheumatoid arthritis, 1 systemic vasculitis, 1 Sjögren's syndrome, 1 Behçt's disease), 4 a neurologic disorder (3 multiple sclerosis, 1 myasthenia), 3 a haematologic disease (2 pure red cell aplasia, 1 autoimmune thrombocytopenia), 2 had a gastrointestinal disease (1 Crohn's disease, 1 autoimmune enteropathy) and 1 had a multiple autoimmune disorder. There was no regimen-related toxicity and no opportunistic infections occurred. Ninety percent of the patients improved and/or had a complete remission after the procedure. Fifty percent of the subjects went into complete or partial remission after a median follow-up of 15 months (range 3-25) while 50% relapsed after a median follow-up of 11 months, (range 6-16). The incidence of relapse in the group treated with fludarabine was lower (30%). INTERPRETATION AND CONCLUSIONS: A non-myeloablative conditioning regimen was able to induce persistent remission in some patients with severe autoimmune diseases. There was no mortality or morbidity related to the procedure. The extent of remission does, however, remain to be established.

Adolescent↗