Antilactoferrin antibodies in autoimmune liver diseases

OBJECTIVE: Lactoferrin, an immunoregulatory protein in mucosal secretions, is one of the target antigens to perinuclear antineutrophil cytoplasmic antibodies (P-ANCAs). Circulating lactoferrin is cleared in the liver, but little is known about the implication of lactoferrin in hepatic inflammation. To evaluate the implication of immunological response to lactoferrin, we examined antilactoferrin antibodies in autoimmune liver diseases. METHODS: Fourteen patients with primary biliary cirrhosis (PBC), 14 with autoimmune hepatitis (AIH), five with autoimmune cholangitis (AIC), six with chronic hepatitis C, and five with chronic hepatitis B were studied. We evaluated autoantibodies to lactoferrin in the sera of the patients by the Western Immunoblotting method. RESULTS: Sera of five of the 14 patients (35.7%) with PBC, four of the 14 patients (28.6%) with AIH, and five of the five patients (100%) with AIC contained autoantibodies to human lactoferrin, but none with hepatitis B or C had them. The higher prevalence of serum antibodies to human lactoferrin was shown to be higher in patients with AIC than with hepatitis B (p < 0.01), hepatitis C (p < 0.01), PBC (p < 0.05), and AIH (p < 0.05). CONCLUSION: Lactoferrin located in bile ducts and liver cells is one of the candidates of target antigens in autoimmune liver diseases, especially in AIC.     

Autoimmune liver diseases: the relation to other autoimmune pathology

Nebraska Hospital Market Areas (HMAs) with significantly and consistently high admission rates for Ambulatory Care Sensitive Conditions (ACSC) were identified using the Blue Cross and Blue Shield of Nebraska (BCBSN) small area analysis data. Two-thirds of those hospitalized were surveyed by Wiese Research of Omaha, Nebraska to determine if the cause for the high admission rates was related to outpatient care quality. BCBSN members living in HMAs without high admission rates were also surveyed for comparison purposes. The survey revealed that satisfaction with outpatient care was high, and that access (geographic or financial) was not a problem for either the test or control group. The test group did delay (for a short time) obtaining outpatient care when compared to the control group. Most of the control group stated that they obtained outpatient care the day symptoms started. Although the majority of the test group obtained outpatient care within a week, they were not as prompt in obtaining outpatient care as the control group. The types of conditions studied (ACSCS) are conditions that can rapidly become severe, therefore prompt treatment is imperative. The main reason given for chronic delays of both groups were that the condition "suddenly became serious." There may be implications for providers to use more "compliance-gaining" strategies in problem area, and for insurers to offer contract endorsements which would encourage members to obtain prompt treatment and preventive healthcare.     

Incidence and prevalence of eye cancer

A three and one half-year-old female with Melnick-Needles osteodysplasia is presented. In addition to the characteristic bone roengenograms and obstructive uropathy, the patient had inadequate formation of bone marrow elements and pulmonary arter hypertension.     

Silicone and autoimmune diseases

BACKGROUND AND PROCEDURE: The etiology of familial hemophagocytic lymphohistiocytosis (FHL), which is characterized by fever, hepatosplenomegaly, pancytopenia, and coagulopathy, remains unknown. We analyzed 43 FHL patients, all with affected siblings, in 18 families who were identified during the period 1986-1995 in Japan. RESULTS: The presence of consanguinity was evident in two families (11%). The majority of families lived in western Japan, where the frequency of consanguineous marriage is high. The incidence of FHL was significantly higher in the western island, Kyushu, than in other areas. The segregation ratio calculated for these families was 0.35 by the Weinberg proband method, showing the autosomal-recessive inheritance of the disease. Since the diagnosis of an FHL patient without affected siblings (sporadic case) is quite difficult, we calculated the possible number of sporadic cases; approximately 122 patients could be identified as sporadic FHL cases during the same period in Japan. Most of the clinical and laboratory findings were not distinguishable from those of other types of lymphohistiocytosis. However, atypical lymphoid cells with azurophilic granules in peripheral blood were observed in half of the patients at diagnosis, suggesting the clinical importance of this parameter for early diagnosis. Despite intensive therapy, the prognosis of FHL was extremely poor; but 4 of the 8 patients who have survived had received bone marrow transplantation (BMT), indicating the effectiveness of BMT for this disorder. CONCLUSIONS: The distribution of FHL in areas of highly frequent consanguineous marriage and the segregation analysis indicated a genetic factor in FHL. The identification of the genes for FHL is expected to contribute to a cure for this disorder, and might also enable FHL carrier detection and donor selection for BMT.     

Dyslipidemias and autoimmune diseases

The paper summarizes the results of over 30-year studies dealt with dyslipidemias and autoimmune diseases. The teaching of the antiphospholipid syndrome (APS) has aroused interest in the problem. The experience gained shows changes in the blood cholesterol transport system. Patients with systemic lupus erythematosus (SLE) have higher levels of low density lipoprotein cholesterol and lower concentrations of high density lipoprotein (HDL) cholesterol, apolipoprotein A than the controls. The quantitative and qualitative changes in particles result in decreased acceptance of cholesterol from the membrane of a cell and tissues, which promotes the development of vascular diseases. Lipoprotein (a) may be an additional risk factor for thrombosis chiefly of coronary arteries, in patients with SLE and APS. Increased levels of oxidized low density proteins having atherogenic activity were found mainly in patients with SLE. The use of corticosteroids causes the changes in the spectrum of blood lipids, which together with other factors (thrombosis, vasculopathy, thrombocytopenia, etc.) create good conditions for the development of atherosclerosis, which determines the necessity of correcting the parameters of blood lipid transport not only to prevent vascular disorders but to improve the general life prognosis in SLE patients.     

GB virus C/hepatitis G virus infection in autoimmune liver diseases

Cutaneous necrosis may occur as a complication of treatment with interferon. Here we report the first case of cutaneous necrosis developing in a patient receiving interferon alpha-2b for the treatment of chronic hepatitis C viral infection. The patient developed two necrotic lesions while receiving high doses of interferon. We suggest that discontinuation of treatment may be necessary to permit healing of such lesions. Although the exact mechanism involved in cutaneous necrosis remains unknown, our observations support earlier findings suggesting that intraarterial injection may be a factor.     

Prolactin in autoimmune diseases

The immune system is still regarded by many as autonomous, and prolactin (Prl) has traditionally been considered as a lactogenic hormone. Over the last 10 years, the total number of publications considering Prl is decreasing, while the number of those investigating its role in immunity sustainly increased. In addition to the pituitary gland, Prl-like peptides can be produced by activated leukocytes and fibroblasts. Elevated serum levels of Prl in (rat) adjuvant arthritis, (murine) collagen type II-induced arthritis, (murine and human) systemic lupus erythematosus (SLE), and (murine and rat) autoimmune type I diabetes may influence the outcome of the disease. It is suggested that mild hyperprolactinemia is a risk factor for the development of autoimmunity. This can occur under certain circumstances, for example adrenocortical deficiency or postpartum. In human SLE, Prl appears to favor the production of anti-double stranded DNA. While glucocorticoids would damp the immune reactivity, Prl constitutes a stimulatory link between the neuroendocrine and immune systems. Future directions should include: 1) multicenter projects for evaluation of the therapy with Prl-inhibiting compounds in SLE, considering for example the HLA-DRB1 *0301 status; and 2) the regulation of extra-pituitary Prl-like cytokines ("proliferins") (e.g., in rheumatoid arthritis synovium) and their role in the production of catabolic enzymes.     

Incidence and prevalence of lameness in dairy cattle

A survey was made of 37 dairy farms in Wirral, mid-Cheshire, mid-Somerset and Dyfed, Wales, to assess the incidence and prevalence of lameness in the cows between May 1989 and September 1991. The incidence was obtained from records made whenever a cow was examined for lameness or received preventive foot-trimming. The mean annual incidence was 54.6 new cases per 100 cows with a range from 10.7 to 170.1 and the mean values during summer and winter were 22.9 and 31.7, respectively. The prevalence of lameness was measured by regular visits at which locomotion was scored on a scale of 1 to 5, and the prevalence of lameness was calculated for each visit as the proportion of cows with scores of 3 or more. The mean annual prevalence over the whole period was 20.6 per cent with a range from 2.0 to 53.9 per cent for the 37 farms. The mean prevalences during summer and winter were 18.6 and 25.0 per cent, respectively. The prevalence measured at a single visit in midsummer or midwinter was significantly correlated with the mean prevalence over the whole corresponding period and may be useful as an assessment of the extent of lameness in a herd and the efficacy of control measures. There was evidence that training farmers to recognise early cases of lameness and request veterinary treatment resulted in a marked reduction in the duration of cases of lameness.     

Molecular mechanism of autoimmune diseases

When a new technology bursts on the horizon and reenergizes a field that has seemed to be flagging, as minimally invasive surgery has done for the field of general surgery, many enthusiasts rapidly embrace the discipline. Questions should arise, however, as to what novelty has really been introduced, where it should fit in our treatment of patients, and, when the dust settles, what alternatives truly have been provided to the advantage of our patients. This article provides information and data about some of these procedures, while trying to address these issues and answer some questions that new technology raises.     

Diabetes and autoimmune diseases. I

An account is given of the clinical and serological associations between diabetes and autoimmune diseases, especially those between diabetes and antihyperoglobulin, antithyroid, anti-intrinsic factor, anticorticoadrenal cell, and anti-nucleic acid autoantibodies. Body fluid antipancreas autoimmunity is examined from various standpoints relating to antipancrease cell antibodies (ICA), autoantibodies against glucagon-secreting cells (ECA) and somatostatin-secreting cells (SCA), and anti-islet cell surface antibodies (McLaren and Lernmark antibodies). Particular attention is directed to ICAs, since these have supplied the background for the recent division of type I diabetes into Ia viral and Ib autoimmune. Stress is laid on both the soundness and the problems forming part of ICAs, since their actual pathogenetic role (cytoplasmic markers?) still has to be determined, even though their persistent and significant association with autoimmune polyendocrinopathies is certain.     

Incidence and prevalence of different uveitis entities in Finland

A prospective, open, multicentre study was performed to investigate the efficacy and safety of long-term treatment with cyclosporin in adults with severe atopic dermatitis. Subjects were treated for a maximum of 48 weeks. For the first 8 weeks, cyclosporin was administered at 2.5 mg/kg per day. The dose was then adjusted according to response. Disease activity was monitored using the six-area, six-sign score and the proportion of skin involved. Pruritus and sleep disturbance were assessed using four-point scales. Response was further evaluated on a five-point scale. Adverse events, blood pressure and serum biochemistry were monitored. Tolerability was assessed on a five-point scale. One hundred subjects were enrolled and 65 completed 48 weeks of treatment. Withdrawals occurred due to remission (three), inadequate response (seven), protocol violations (11) and adverse events (14, of which seven were probably treatment related). Cyclosporin produced rapid and highly significant improvements in all indices of disease activity. Sixty-five subjects considered that they had shown a considerable improvement or complete clearance of disease. Most patients relapsed after cessation of treatment, but neither signs nor symptoms had returned to baseline severity 8 weeks later. Blood pressure and serum creatinine levels increased slightly, and in one subject renal impairment was a major factor contributing to withdrawal of the drug. Overall, 85 subjects rated the tolerability of cyclosporin as good or very good. The results indicate that cyclosporin has a place in the long-term treatment of severe atopic dermatitis provided that appropriate patients are selected and careful monitoring is performed.     

Gene therapy in autoimmune diseases

The influence of "shinrin-yoku" (forest-air bathing and walking) on blood glucose levels in diabetic patients was examined. Eighty-seven (29 male and 58 female) non-insulin-dependent diabetic patients [61 (SEM 1) years old] participated in the present study. Shinrin-yoku was performed nine times over a period of 6 years. The patients were divided into two parties. They then walked in the forest for 3 km or 6 km according to their physical ability and/or the existence of diabetic complications. The mean blood glucose level after forest walking changed from 179 (SEM 4) mg.100 ml-1 to 108 (SEM 2) mg.100 ml-1 (P < 0.0001). The level of glycated haemoglobin A1c also decreased from 6.9 (SEM 0.2)% (before the first shinrin-yoku) to 6.5 (SEM 0.1)% (after the last shinrin-yoku; P < 0.05). Blood glucose values declined by 74 (SEM 9) mg.100 ml-1 and 70 (SEM 4) mg.100 ml-1 after short- and long-distance walking respectively. There was no significant difference between these values. Since the forest environment causes changes in hormonal secretion and autonomic nervous functions, it is presumed that, in addition to the increased calorie consumption and improved insulin sensitivity, walking in a forest environment has other beneficial effects in decreasing blood glucose levels.     

Cardiovascular manifestations of systemic autoimmune diseases

The systemic autoimmune diseases are a protean group of illnesses that primarily affect the joints, muscles, and connective tissue. All aspects of the cardiovascular system can be involved with clinical consequences ranging from asymptomatic abnormalities to serious life-threatening conditions. This article discusses the cardiovascular manifestations of the systemic autoimmune diseases with particular focus on clinical pathophysiology and management.     

Nerve growth factor and autoimmune rheumatic diseases

The effect of intestinal lymph on blood pressure in rats was observed by the methods of lymph drainage and lymph infusion. The results obtained are as follows: (1) After 150 min of the lymph drained through the cannula of intestinal lymph duct, the blood pressure was significantly lower than that of the sham group (P < 0.05). (2) Equivalent albumin or intralipid infusion was not able to prevent the decrease in blood pressure when the lymph was lost. But in jugular-intestinal lymph duct shunt group, no significant blood pressure decrease could be seen during the drainage procedure for 4 h. (3) The blood pressure of rat with serious hemorrhagic shock could be increased significantly with a little amount of intestinal lymph infusion, and the rats survived longer than those of the control group (P < 0.05-0.01). The above results suggest that the intestinal lymph may play an important role in maintenance of blood pressure, in addition to the known function of lymphatic system by returning tissue fluid to blood and maintaining circulating blood volume.     

Radiologic manifestations of the systemic autoimmune diseases

Advances in thoracic imaging during the past two decades, such as CT scans and MR imaging, have enhanced our understanding of the pleuropulmonary abnormalities that develop in the systemic autoimmune diseases. In this article, the thoracic radiologic manifestations of several connective tissue diseases (systemic lupus erythematosus, rheumatoid arthritis, Sj?gren's syndrome, polymyositis/dermatomyositis, progressive systemic sclerosis, and anklyosing spondylitis), two granulomatous vasculitides, (Wegener's Granulomatosis and Churg-Strauss syndrome), and antiglomerular basement membrane disease are reviewed.     

Incidence and prevalence of symptomatic celiac disease among adults in Denmark

The purpose was: 1) to determine annual incidence rates of adult coeliac disease, 2) to calculate the risk of having developed coeliac disease in adult life, and 3) to calculate the life time prevalence by five-year birth cohorts. All patients fulfilling defined criteria for adult coeliac disease living in the county of Copenhagen and diagnosed during the years 1976-1991 were included. The reference population consisted of 503,283 subjects. The overall incidence had been stable during the period, and was 1.27/10(5). The figures for females and males were 1.55/10(5) and 0.96/10(5), respectively (p = 0.04). The median (range) age at the time of diagnosis was 40.1 (16-81). Age specific incidence rates varied considerably, with the peak rate located in the middle-aged population. The incidence rates were influenced by age at diagnosis (p = 0.01) and sex (p = 0.04), but not by the year when diagnosed. For a subject aged 89 years, the risk was 0.88/1000. The overall prevalence was 45.9/10(5). In conclusion, this incidence/prevalence is one of the lowest reported, and is definitely lower than prevalences reported from our neighbouring Scandinavian countries. Nothing points to higher incidence rates being present in Danish adults to compensate for the previously demonstrated very low rates in Danish children.     

An imbalance between Th1 and Th2-like cytokines in patients with autoimmune diseases--differential diagnosis between Th1 dominant autoimmune diseases and Th2 dominant autoimmune diseases

An imbalance between T helper cell (Th)1 and Th2-like cytokines has been described in several autoimmune diseases. Organ specific autoimmune diseases such as multiple sclerosis (MS) and inflammatory bowel diseases (IBD) are caused by Th1 dominant immune responses. On the contrary, systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and Sj?gren's syndrome(SS) are characterized by Th2 dominant imbalance of cytokine production. It might be useful for differential diagnosis among patients with various autoimmune diseases such as SLE, SS, IBD, and MS to measure the serum levels of cytokines such as IL-10, IFN gamma, and TNF alpha using ultrasensitive enzyme-linked immunosorbent assay system.