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HLA, complement C2, C4, properdin factor B and glyoxalase types in South Indian diabetics.

A series of diabetic patients from 3 centres in South India have been tested for HLA A, HLA B, BF, C2, C4A, C4B and GLO types. For insulin-dependent diabetes mellitus (IDDM) patients there was a significant increase in HLA B8, of BF F and decrease of C4 A6. No significant variation in HLA, BF, C2 or GLO frequencies was found in non-insulin-dependent diabetes mellitus (NIDDM) patients, but there was a significant decrease in C4B 1 and an increase in C4B 2. The HLA and BF association in South Indian IDDM patients is very different from that reported previously in North India.

Adolescent↗

Human complement component C4. Structural studies on the fragments derived from C4b by cleavage with C3b inactivator.

1. One of the activation products of C4, C4b, was prepared, and the reactive thiol group on the alpha'-chain was radioactively labelled with iodo[2-14C]acetic acid. The alpha'-chain was isolated and the N-terminal amino acid sequence of the first 13 residues was determined. 2. C4b was cleaved by C3bINA in the presence of C4b-binding protein and C4d and C4c isolated. The radioactive label and therefore the reactive thiol group were located to C4d. 3. C4c was reduced and alkylated and the two alpha'-chain fragments of C4c were separated. 3. The molecular weights, amino acid analyses and carbohydrate content of the three alpha'-chain fragments were determined. C4d has a mol.wt. of 44500 and a carbohydrate content of 6%. The two alpha'-chain fragments of C4c have mol.wts. of 25000 (alpha 3) and 12000 (alpha 4) and carbohydrate contents of 10 and 22% respectively. 4. The N-terminal amino acid sequences of C4d, the alpha 3 and the alpha 4 fragments were determined for 18, 24 and 11 residues respectively and, by comparison with the N-terminal sequence of the C4b alpha'-chain, the 25000-mol.wt. fragment (alpha 3) was shown to be derived from the N-terminal part of the alpha'-chain. 5. C-Terminal analyses were done on the alpha'-chain and its three fragments. Arginine was found to be the C-terminal residue of C4d and of the alpha 3 fragment. The C-terminal residue of the alpha'-chain and of the alpha 4 fragment could not be identified. The order of the three fragments of the alpha'-chain is therefore: alpha 3(25000)--C4d(44500)--alpha 4(12000). The specificity of C3bINA is for an Arg--Xaa peptide bond.

Amino Acid Sequence↗

Complement (C3, C4) consumption in cardiopulmonary bypass, cardioplegia, and protamine administration.

Anaphylatoxins produced by complement activation have been postulated to be responsible for postperfusion syndrome and protamine hypotension in patients undergoing cardiac surgical procedures. The consumption of serum complement components C3 and C4, which reflects the classic and alternate pathway activations of the complement system, was studied in 22 patients undergoing cardiac operations. Prior to the onset of cardiopulmonary bypass, the complement levels were within normal range. Rapid reduction in both C3 and C4 within minutes of cardiopulmonary bypass indicated rapid complement activation. Such a reduction in complement levels could not be accounted for by either hemodilution or transfusion of complement-poor blood. Aortic cross-clamping and cold potassium cardioplegia followed by myocardial reperfusion did not lead to further consumption of C3 and C4. Slow intravenous infusion of protamine sulfate after cardiopulmonary bypass did not change C3 and C4 levels significantly in our patients, although protamine and heparin-protamine complex have been shown to activate complement components in vitro. In another group of 9 similar cardiac surgical patients, C3 and C4 were found to return to normal levels within 24 hours after operation. This study thus confirms the rapid activation of the complement system by cardiopulmonary bypass but fails to demonstrate further activation of the complement system by cardioplegia or protamine administration.

Adult↗

[Calorie requirement after major abdominal surgery (author's transl)].

After major abdominal surgery 32 patients received a parenteral nutrition for 6 days with 360 g of a carbohydrate mixture (levulose:glucose:xylitol = 2:1:1) and 100 g of an L-amino acid mixture/24 h. 16 patients with benign disease showed positive nitrogen balances, 16 patients with malignant diseases balanced or slightly negative nitrogen balances. Postoperatively, blood glucose levels did not require insulin. Less than 1.5% of the infused levulose, 2.0% of glucose and 2.4-4.1% of xylitol were found in urine. C3- and C4- complement levels in serum were below normal, transferrin showed a pathological decrease in carcinoma patients.

Abdomen↗

Effect of moderate malnutrition on immediate hypersensitivity and immunoglobulin E levels in asthmatic children.

Dermal reactions and IgE levels were compared in 51 asthmatic Colombian children identified on the basis of anthropometric measurements as nutritionally normal (25) or mildly (16) or moderately (10) undernourished. Twenty-five nonatopic children served as controls. Total serum IgE concentrations were significantly elevated in the asthmatic group as a whole. Moderately malnourished (grade II) asthmatic children had more than twice as much serum IgE as normal or mildly malnourished (grade I) asthmatic subjects and seven times more than nonatopic children. Intestinal parasitism did not appear to contribute to these differences in IgE levels. Serum levels of IgA and IgD were similarly elevated in grade II asthmatics. Concentrations of serum IgG, IgM, and C3 and C4 complement were unaffected by nutritional or allergic status. Eosinophilia in nasal mucus was significantly reduced in grade I and grade II malnourished asthmatic children. Among asthmatics, the most frequent dermal reactions were to mite antigens (96%), house dust (67%), and grass pollens (35%). Significant levels of specific IgE were detected by the RAST to two species of mites in nearly all atopic children. There was no apparent influence of nutritional status on the distribution of reactivity or specific IgE assay. The clinical significance of hyperimmunoglobulin E in atopic, moderately malnourished children remains to be elucidated.

Adolescent↗

Humoral and cellular immune parameters in untreated and phenytoin-or carbamazepine-treated epileptic patients.

The peripheral blood lymphocyte subsets, serum immunoglobulins (Ig A, G, M), and C3 and C4 complement protein concentrations were determined in 40 healthy subjects, 30 phenytoin-treated, 22 carbamazepine-treated and 38 untreated epileptic patients. The levels of beta-lymphocytes, IgM and C3 complement proteins were found to be significantly higher in untreated epileptics than in healthy controls (P < 0.01, P < 0.02 and P < 0.05, respectively). The absolute number of beta-lymphocytes appeared to be unaffected by phenytoin or carbamazepine treatment; however, IgM levels were significantly lower in carbamazepine-treated patients than both epileptic (P < 0.01) and healthy (P < 0.05) controls. Phenytoin-treated patients had a significant reduction in the mean IgA and IgG levels compared to healthy and epileptic controls (P < 0.05). With both drug treatments, significantly lower T-suppressor lymphocyte counts and thus higher T-helper to T-suppressor lymphocyte ratios were observed with respect to healthy and epileptic controls. Our results demonstrate that while phenytoin decreases serum IgA and IgG levels, carbamazepine reduces IgM levels significantly, and untreated epileptics show immune profiles significantly different to those of healthy subjects, suggesting that epilepsy per se may be associated with certain immune aberrations induced by antiepileptic drugs.

Adolescent↗

Immunopathogenic mechanisms in hypertension.

There is a growing interest in immunologically-mediated lesions in the cardiovascular system, as there has been evidence that there are antimitochondrial antibodies (AMA) in patients with hypertrophic cardiomyopathy or hypertensives with left ventricular hypertrophy (LVH). We have also very recently published findings from our laboratory that hypertensives with LVH have a considerable quantity of anticardiac antibodies (ACA) in their serum. The aim of this study was to investigate the possible involvement of autoimmune mechanisms in the pathogenesis and evolution of hypertensive disease. Three groups of subjects were included in the study. Group A comprised 37 patients (20 men, 17 women, mean age 50.5 +/- 8.5 years) with mild to moderate essential hypertension, 19 without echocardiographic evidence of LVH, and 18 with LVH. Group B comprised 10 patients (6 men, 4 women, mean age 45.1 +/- 8.7 years) with secondary hypertension. The control group (C) comprised 15 normotensive subjects (8 men, 7 women, mean age 47.7 +/- 8.7 years). Cellular immunity against arterial wall antigen was studied in all subjects by means of migration inhibitory factor (MIF) against relevant antigen preparation. Sera from Group A and C subjects were tested for the presence of autoantibodies against both specific (myocardial) and nonspecific antigens, by means of the indirect immunofluorescence technique. Eighty per cent of patients with essential hypertension showed a positive cellular response (MIF) against an arterial wall antigen compared to the patients with secondary hypertension or the control group. Moreover, patients with essential hypertension and LVH had the highest incidence of specific (anticardiac, ACA) and nonspecific autoantibodies and the highest C3c and C4 complement component levels compared to patients without LVH or the control group. Most of the ACA positive patients were also AMA positive, while the ACA negative patients were AMA negative as well. Defects in cell-mediated immunity against arterial wall antigen(s) may be the cause or the effect of hypertension. On the basis of our findings that there was no delayed type hypersensitivity response to arterial wall antigen(s) in the patients with secondary hypertension, we suggest that, in some cases of essential hypertension, delayed hypersensitivity reactions possibly contribute to the pathogenesis of hypertension. Autoimmune mechanisms are discussed on the basis of common epitopes shared between heart and arterial tissue.

Autoantibodies↗

Cicatricial alopecia; a dermatopathologic and immunopathologic study of 33 patients (pseudopelade of Brocq is not a specific clinico-pathologic entity).

BACKGROUND: Pseudopelade of Brocq (PB) is a permanent progressive scarring alopecia characterized by numerous alopecic patches localized only in the scalp, that tend to coalesce into larger, irregular plaques with policyclic borders. PB can be considered either the final atrophic stage of several scarring disorders such as lichen planus pilaris (LPP) and discoid lupus erythematosus (DLE) (secondary PB) or an autonomous disease (primary PB). The aim of this study was to assess the incidence of primary vs. secondary PB by a combined histopathological and immunopathological study in a series of patients who fulfilled the clinical diagnostic criteria for PB set forth by Braun Falco et al. METHODS: We studied 33 patients (5 males and 28 females, whose age ranged from 24 to 75 years). The duration of the disease (from onset to biopsy) ranged from 3 months to 8 years. Serum samples were tested for circulating auto-antibodies (antinuclear antibodies anti ENA, anticentromere, anti-Scl70, antithyroid, antigastric parietal cells) circulating immune complexes, total and single fraction (C3, C4) complement activity. The skin biopsies taken from the active advancing margin of the more recent alopecic patch were bisected vertically, one was sent for histopathological examination, and the other for the immunofluorescence studies. RESULTS: In all patients the serum tests above were found to be negative or normal. Histopathologically, 11 biopsies (33.3%) displayed findings typical for LPP whereas seven cases (21.2%) showed typical DLE features. In the remaining 15 cases (45.5%) histopathological findings were not suggestive of any specific dermatosis. DIF investigations showed findings typical of LPP in six cases (18.1%) and typical of DLE in seven cases (21%). In three cases we did not find findings typical of LPP, DLE, or any other specific dermatitis. In 11 cases no immunological deposits could be detected and therefore were classified as negative. CONCLUSION: In conclusion, PB is a type of scarring alopecia of the scalp associated with a peculiar clinical presentation and evolution, which cannot be considered an autonomous nosologic entity because in 66.6% of patients it is the end stage of other inflammatory chronic diseases such as LPP and DLE. It is conceivable that even in those cases in which the histopathological and immunopathological findings did not allow for a specific diagnosis, LPP and DLE were also involved. It is noteworthy that in our study the histopathological and the immunopathological examinations did not conflict and often the results were even coincidental, thus confirming the compatibility of the combined histo-immunopathological approach in the diagnostic evaluation of PB.

Adult↗

T cell deficiency in patients with autoimmune hemolytic anemia ('warm type').

19 patients with chronic 'warm type' autoimmune hemolytic anemia were studied for abnormalities of cellular immune reactions. Evidence was obtained for a reduction of rosette-forming cells (RFC). Lymphocytotoxic antibodies were present in only 8 patients and correlated, with only one exception, with a reduced number of RFC. No significant deviation from normal ranges of the three major immunoglobulin classes in the patients' sera were found. C3 and C4 complement components were also, with one exception, within normal limits. In 18 of 19 patients no apparent association existed between the type or the amount of autoantibodies and/or complement components fixed on red cells and the levels of the respective immunoglobulins or complement in the sera.

Anemia, Hemolytic, Autoimmune↗

Immunological parameters in Alzheimer's pre-senile dementia.

Serum immunoglobulin levels and C3 and C4 complement concentrations were assayed and serum tested for the presence of autoantibodies in 17 patients with pre-senile Alzheimer's disease. The majority of patients showed a reduced level of one or more of immunoglobulins IgG, IgA or IgM. No significant abnormality was found to indicate an autoimmune disorder.

Aged↗

Long term efficacy of high-dose intravenous methylprednisolone pulses in active lupus nephritis. A 21-month prospective study.

The efficacy of a single course of three high dose intravenous (i.v.) methylprednisolone (MP) pulses followed by low dose oral prednisone (PRED) was assessed in a group of patients with active lupus nephritis (LN). At 21 months after such therapeutic regimen in 10 out of 12 patients a complete clinical remission was found, in one patient a partial response with persistent moderate renal failure occurred, while one patient was refractory even to the additional administration of cyclophosphamide. The statistical analysis of repeated measures of a series of biological markers of LN, monitored over the course of the study, evidenced a significant improvement of serum creatinine (p < 0.05), C3 and C4 complement components (p < 0.05), 24-hour proteinuria (p < 0.02) and ESR values (p < 0.05). Moreover, a progressive and significant reduction of mean daily PRED dosage was reported (p < 0.05). We conclude that i.v. MP pulse therapy may exert a substantial long-term control of active LN and may induce steroid-sparing effects.

Administration, Oral↗

[Protein markers in evaluation of nephroprotective effects of antihypertensive drugs in patients with arterial hypertension].

Fifty patients with stable slight and moderate uncomplicated essential hypertension, treated by ramipril, atenolol, or isradipine, were examined. Total protein and urinary excretion of individual proteins were studied before and after treatment. Urinary concentrations of apolipoproteins A1 and B1, alpha 1-acid glycoprotein, alpha 1-antitrypsin, prealbumin, albumin, beta 2-microglobulin, transferrin, haptoglobin, IgG and IgA, and C3 and C4 complement components were measured. Index of proteinuria selectiveness was calculated for each portion of urine. All three drugs exerted a nephroprotective effect, atenolol being the most active of them. Apolipoproteins, IgG, and complement components were the most valuable for diagnosis. Their excretion correlated with the severity of arterial hypertension and efficiency of treatment. Use of protein markers helps reliably assess the renal function and monitor the treatment efficiency.

Adult↗

[Characterization of immunological parameters of the lacrimal fluid in patients with various types of the course of keratoconus].

Local immunity is analyzed in 81 patients (146 eyes) aged 16-49 years with three clinical patterns of keratocone. During long remission, IgG level was the maximum. In progressive disease, sIgA and transferrin levels were increased. The most pronounced shifts were detected in the patients with acute keratocone: increased concentrations of IgM, C3 and C4 complement components, alpha 1-antitrypsin, orosomucoid, lysozyme activity, and immune complexes. These data prompt the development of pathogenetically based approaches to the treatment of patients with various clinical immunological types of keratocone.

Acute Disease↗

Efficacy of hyperbaric oxygenation in atopic dermatitis.

Ten patients (5 with atopic dermatitis and 5 with asthma-prurigo) aged 8-38 years, were treated with hyperbarie oxygenation, at the Institute of Maritime and Tropical Medicine. Daily one exposure was applied at 0.1 MPa pure oxygen, during 15 days. Parallelly to the clinical evaluation also G, M, E immunoglobulins and the level of C3 and C4 complement were determined. All patients given this treatment improved clinically. In 9 of them, the level of IgE immunoglobulin decreased. The complement levels also decreased.

Adolescent↗

[Diagnostic and prognostic value of the assessment of selected indicators of humoral immunity in alcoholism-related pathology of the liver].

The purpose of the study was evaluation of the usefulness of selected indices of humoral immune responsiveness in the differential diagnosis of post-alcoholic hepatocellular damage. The study was carried out in 105 patients: 10 patients with a history of alcohol abuse without clinical and biochemical evidence of hepatocellular damage, 2) patients with alcoholic cirrhosis, 3) patients with post-inflammatory cirrhosis. The prognostic usefulness of the determinations of serum IgM, C3 and C4 complement components and circulating immune complexes in early diagnostic of alcoholic liver disease was demonstrated. It was noted also that increased serum IgA level may be a useful index differentiating of cirrhosis after hepatitis from alcoholic cirrhosis.

Alcoholism↗

[Immunological profile of workers occupationally exposed to chlorine].

Immunological profile of 42 men working under exposure to chlorine for a period from 2 to 38 years was analysed. Toxicological analyses of air samples which were carried out for 20 years showed similar chlorine concentration ranging from 0.21 to 1.05 mg/m3. The number of B, T, and non-B, non-T lymphocytes was determined as well as the C3c, C4 complement components and proteins of acute phase reaction: alpha 1-acid-glycoprotein, haptoglobin and ceruloplasmin in the serum. Chronic exposure to chlorine produced a stimulating effect on the immune system, which was manifested by elevated IgA, IgD and IgM levels, the concentration of acute phase reaction proteins and increased number of B lymphocytes. The observed phenomenon had no influence on the antibacterial and anticancer immunity of the workers.

Adult↗

[Familial studies of patients with hereditary angioedema].

25 families with 607 members were studied. 165 persons of them suffer from hereditary angioneurotic edema and 28 persons had died from this disease. The clinical forms of the disease are discussed. A classification of angioneurotic edema caused by C-inactivator deficiency is presented. The importance of the examination of C1 inactivator (quantitatively and qualitatively) and of C4 complement fraction in patients with hereditary angioneurotic edema is pointed out.

Adolescent↗

[Ischemic heart disease--clinical, biochemical and immunobiological parallels].

In patients with various forms of ischemic heart disease the following indices were examined by radial immunodiffusion: alpha-1-acid glycoprotein, alpha-1-antitrypsin, haptoglobin, alpha-2-glycoprotein, beta-2-glycoprotein, immunoglobulin, C3 and C4 complement fractions. The changes in the serum glycoproteins during the acute phase of myocardial infarction are pointed out. The changes in the immunoglobulins and the complement fractions in patients with ischemic heart disease are discussed. Their determination in patients with stenocardia and past myocardial infarction is of no diagnostic value.

Angina Pectoris↗