Thymoma with immunodeficiency (Good's syndrome) associated with myasthenia gravis and benign IgG gammopathy.

We treated a case of thymoma with immunodeficiency (Good's syndrome) associated with a rare combination of other parathymic syndromes including myasthenia gravis, benign IgG lambda M component, pernicious anemia, and diabetes. The characterization of the patient's immunologic capacity disclosed practically normal T-cell number and mitogenic responses but impaired lymphokine production as well as B-cell function.

Cell-mediated immunity in untreated and PUVA treated atopic dermatitis.

In 22 adult patients with atopic dermatitis, lymphocyte subpopulation counts, mitogenic responses to several PHA and Con A concentrations, nonspecific mitogen induced, and indomethacin sensitive suppressor cell functions and leukocyte migration inhibitory factor production were investigated. Patients with severe atopic dermatitis had normal PHA and Con A responses, although somewhat lower than matched controls, while mild AD patients equalled controls in this respect. No significant differences between AD patients and controls were detected with respect to lymphocyte subpopulations, suppressor cell function or leukocyte migration inhibitory factor production. Methoxalen plus ultraviolet light (PUVA) therapy induced significant clinical improvement in 9 out of 10 treated patients. A concomitant decrease of the mitogenic responses and increase of the Con A induced nonspecific suppressor cell activity was recorded, while other immunological parameters remained unaffected by the therapy. Thus PUVA therapy induces both local clinical and systemic immunological manifestations. The possibility that the observed immunological changes would be operative in the PUVA induced healing process, however, seems unlikely, as the present study did not disclose any obvious relationship between immune parameters and severity of atopic dermatitis.

Unusual association of hyperkalemia and hypertension.

We report an unusual association of hyperkalemia, mild hyperchloremic acidosis, and hypertension in a young woman. Pseudohyperkalemia, Addison's disease, renal insufficiency, classical hyporeninemic hypoaldosteronism, isolated hypoaldosteronism, and iatrogenic causes were excluded. The patient's findings were compatible with a rare syndrome designated as type II pseudohypoaldosteronism, Gordon's syndrome.

Concanavalin A induced and spontaneous suppressor cell capacity of newborn and fetal lamb lymphocytes.

Concanavalin A induced newborn lamb blood lymphocytes suppress the proliferation of adult lymphocytes to the same magnitude as similarly induced adult suppressor cells. Concanavalin A induced suppressor capacity of fetal spleen cells at term is not as strong as that of newborn peripheral blood lymphocytes. Thymocytes of the same fetuses do not possess any suppressive capacity inducible by this mitogen, but show a spontaneous suppressor capability. Spleen cells exhibit only a low spontaneous activity. Interestingly, when peripheral blood lymphocytes of newborn lambs spontaneously suppress the response of both unrelated and maternal cells, adult lymphocytes enhance the proliferation. These results show that functional suppressor cells are found in both newborn and fetal lambs. Our data also indicate that cells spontaneously suppressive are established in thymus and spleen, whereas cells that can be rendered suppressive by concanavalin A stimulation are found in the spleen. Therefore, the spontaneous thymic suppressor cells may represent a more primitive cell population than those of the spleen.

Effects of retinoic acid, 1,25-dihydroxyvitamin D3, cytosine arabinoside and alpha-interferon on bone marrow cells from patients with myelodysplastic syndromes.

Bone marrow cells from 15 patients with myelodysplastic syndromes and 2 with acute myeloid leukemia were incubated in vitro with all-trans-retinoic acid (RA), 1,25-dihydroxy vitamin D3 (D3), cytosine arabinoside (ara-C) and alpha-interferon (IFN). 3H-thymidine incorporation (3H-TdR), differentiation and clonal growth were studied. D3 was found to be the most effective inducer of differentiation and differentiation was correlated with a decreased 3H-TdR. Differentiation with one of the inducers was significantly correlated to differentiation with any of the other inducers. Patterns of differentiation and spontaneous and D3-induced 3H-TdR were used to divide the patients into 3 different groups. In the first group, 5 patients with extremely low spontaneous 3H-TdR and differentiation in combination with a slightly increased 3H-TdR after induction differed from all other patients by a higher percentage of bone marrow blast and a more pronounced pancytopenia. The two other groups had a high spontaneous 3H-TdR but differed with respect to the D3-induced differentiation which was absent in one group (n = 6) and present in the other (n = 5). The two groups showed no difference in the clinical features.

Effects of 42 months of GH treatment on bone mineral density and bone turnover in GH-deficient adults.

OBJECTIVE: To study the effects of GH treatment for up to 42 months on bone mineral density (BMD) and bone turnover. DESIGN AND METHODS: BMD with dual energy X-ray absorptiometry, serum type I procollagen carboxy-terminal propeptide (PICP), serum type I collagen carboxy-terminal telopeptide (ICTP) and serum IGF-I were assessed in 71 adults with GH deficiency. There were 44 men and 27 women, aged 20 to 59 (median 43) years. Thirty-two patients completed 36 months and 20 patients 42 months of treatment. RESULTS: The BMD increased for up to 30-36 months and plateaued thereafter. In the whole study group, the maximum increase of BMD was 5.0% in the lumbar spine (P<0. 001), 5.9% (P<0.01) in the femoral neck, 4.9% (NS, P>0.05) in the Ward's triangle and 8.2% (P<0.001) in the trochanter area. The serum concentrations of PICP (202.6+/-11.5 vs 116.3+/-5.4 microg/l; mean+/-s.e.m.) and ICTP (10.5+/-0.6 vs 4.4+/-0.3 microg/l) doubled (P<0.001) during the first 6 months of GH treatment but returned to baseline by the end of the study (130.0+/-10.4 and 5.6+/-0.7 microg/l respectively), despite constantly elevated serum IGF-I levels (39. 6+/-4.1 nmol/l at 42 months vs 11.9+/-0.9 nmol/l at baseline; P<0.001). The responses to GH treatment of serum IGF-I, PICP, ICTP (P<0.001 for all; ANOVA) and of the BMD in the lumbar spine (P<0.05), in the femoral neck and the trochanter (P<0.001 for both) were more marked in men than in women. At the end of the study the BMD had increased at the four measurement sites by 5.7-10.6% (P<0.01-0.001) in patients with at least osteopenia at baseline and by 0.1-5.3% (NS P<0.05) in those with normal bone status (P<0.001 for differences between groups; ANOVA). Among patients who completed 36-42 months of treatment, the number of those with at least osteopenia was reduced to more than a half. The response of BMD to GH treatment was more marked in young than in old patients at three measurement sites (P<0. 05-<0.001; ANOVA). In the multiple regression analysis the gender and the pretreatment bone mass appeared to be independent predictors of three measurement sites, whereas the age independently determined only the vertebral BMD. CONCLUSIONS: GH treatment in GH-deficient adults increased BMD for up to 30-36 months, with a plateau thereafter. Concurrently with the plateau in BMD the bone turnover rate normalized. From the skeletal point of view GH-deficient patients exhibiting osteopenia or osteoporosis should be considered as candidates for GH supplementation of at least 3-4 years.

Antibodies against neutrophil cytoplasmic components in Kawasaki disease.

The occurrence of antibodies against neutrophil cytoplasmic components in 39 children (23 boys, 16 girls, median age 2.0 years) with Kawasaki syndrome was studied. The conventional indirect immunofluorescence test (ANC-Ab) on alcohol-fixed neutrophils and two commercially available ELISA tests (ANCA-EIA and MPO-EIA) were employed to detect the antibodies. Fourteen (36%) of the 39 patients with Kawasaki disease had antibodies against neutrophil cytoplasmic components in at least one of the three tests used. Eleven patients were identified using the indirect immunofluorescence test. Five patients were positive in the MPO-EIA test and two additional patients in the ANCA-EIA test. The IF staining pattern was cytoplasmic in eight patients and perinuclear in three. The cytoplasmic staining pattern in patients with acute Kawasaki disease is different from that seen in patients with Wegener's granulomatosis. The occurrence of antibodies may assist in the diagnosis of some patients with Kawasaki disease, although neither the positivity itself nor the five different antibody profiles seem to have any other clinical relevance.

Serum mannan-binding lectin (MBL) in patients with infection: clinical and laboratory correlates.

In this study, we determined the serum levels of mannan-binding lectin (MBL) in patients with suspected or documented infection to characterize the possible role of MBL in the susceptibility to infection. We also investigated the kinetics of MBL during the infection and correlated the concentrations of MBL with those of acute-phase reactants C-reactive protein (CRP) and group II phospholipase A2 (PLA2-II) and cytokines interleukin-1(IL-1). interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha). The frequency of MBL deficiency in the patients with signs of infection did not differ from that of controls. In four patients with MBL deficiency, the infections were caused by common pathogens and the outcome was normal. The mean MBL concentration in the patients with signs of infection was significantly higher than in the healthy controls (9.88 and 4.48 mg/l, respectively; p < 0.05). The highest mean MBL concentration was observed in patients with clinically or microbiologically documented bacterial infection. During follow-up, the MBL concentration altered individually in different patients, but no particular change in pattern in the MBL concentration could be demonstrated in any patient group. Of the acute-phase reactants in the circulation, only CRP and IL-1 showed a weak, albeit significant, negative correlation with the concentration of MBL. In conclusion, the deficiency of MBL was not shown to be an independent risk factor for infection in the adult population studied. The concentration of MBL did not follow the change in pattern of other acute-phase reactants and cytokines during the acute phase response. Therefore, measurement of the MBL concentration as an acute-phase reactant is not useful in the diagnosis or follow-up of infection. On the other hand, the deficiency of MBL can be detected reliably by serological methods even during an infection.

Immune functions in inflammatory bowel and coeliac diseases.

Different immune functions of 10 patients with glutein-sensitive enteropathy (GSE), 9 with Crohn's disease (CD), 11 with ulcerative colitis (UC) and 13 healthy controls were characterized. The numbers of suppressor T cells in GSE were comparable to those of the controls; otherwise, the lymphocyte subpopulations were decreased in these bowel diseases. In the whole-blood cultures, the lymphocyte proliferative responses to PHA were normal in the bowel diseases, but the responses to Con A were decreased in CD. In cultures with D-penicillamine, the inhibition of the helper effect of CD patients was more pronounced in PHA-stimulated cultures than in Con A-stimulated cultures. The total Ig and IgA production did not markedly differ among the groups. PWM-induced IgM secretion was significantly decreased in GSE, CD and UC, and IgG secretion in CD and UC, as compared to controls. In GSE, an increased Con A inducible suppressor cell activity was observed in the IgM production. Altogether, no clear-cut immunological imbalance was detected in any of the bowel diseases; this in agreement with previous works. However, there are some differences in the regulatory cell balance among the patients with GSE, CD and UC. The determination of lymphocyte proliferative responses to PHA and Con A together with D-penicillamine seems to provide a new immunological criterium for distinguishing between Chrohn's disease and ulcerative colitis.

Thyroid antibodies in association with thyroid malignancy. I. Simultaneous occurrence of thyroiditis and thyroid malignancy.

Occurrence of thyroid antibodies and thyroiditis in association with thyroid malignancy, suspected malignancy or other thyroid diseases was studied in 177 patients. Retrospective clinical analysis revealed that 137 patients had thyroid carcinoma (108 papillary carcinomas, 10 occult papillary carcinomas, 14 follicular carcinomas, and 5 other carcinomas) and 40 had other thyroid diseases. Thyroid microsomal (AMC) and thyroglobulin antibodies (ATG) were measured by the particle agglutination method. Clinically significant thyroid antibody titers and histological or clinical features of thyroiditis were seen in nine patients with thyroid carcinoma, being equally prevalent in follicular and papillary carcinomas. Taking into account the prevalence of positive AMC antibodies and thyroid carcinoma in Finland, the highest predicted prevalence of simultaneously occurring thyroid carcinoma and thyroiditis in the under 40 age group should be 0.002% and in the over 40 age group 0.006%. In the present material the observed occurrences in corresponding age groups were unexpectedly high (4.7% and 5.2%). The results may partly be due to patient selection, but they also suggest that there might be a link between thyroiditis and thyroid carcinoma.

Evaluation of the new Behring Nephelometer in the measurement of M proteins.

The Behring Nephelometer is a new automatic analyzer designed for the measurement of specific proteins. The authors evaluated the nephelometer in the determination of M proteins as compared with immunodiffusion and cellulose acetate electrophoresis. In addition, the effects of sample dilution and antigen excess on the nephelometric measurement of M proteins were studied in 24 patient samples containing a single monoclonal IgG, IgA, or IgM M component. Immunodiffusion cannot be recommended for the determination of M proteins. Nephelometry and protein electrophoresis gave similar results with few exceptions. Sera with immunoglobulin monomer-oligomer pairs involve difficulties in serum electrophoresis. In certain cases, special care must be taken to adjust the nephelometric measurement of the M protein to the most accurate part of the calibration curve. All in all, the new Behring Nephelometer proved precise and reliable in M protein determination without risk of antigen excess.

Effect of proctocolectomy on serum antineutrophil cytoplasmic antibodies in patients with chronic ulcerative colitis.

AIMS: To study the effect of proctocolectomy on the antineutrophil cytoplasmic antibody (ANCA) titres in association with ulcerative colitis. METHODS: Serum samples were taken from 15 patients with ulcerative colitis immediately before and at a mean of 24 months after proctocolectomy. Indirect immunofluorescence for ANCA and enzyme immunoassays for myeloperoxidase and proteinase-3 antibodies were employed. A liver biopsy was taken from every patient during the proctocolectomy, and serum liver enzyme activities were also determined. RESULTS: Before proctocolectomy, 13 of the 15 patients had perinuclear antineutrophil cytoplasmic antibodies (p-ANCA). Additionally, one patient had a low tire of classical cytoplasmic ANCA and one had granulocyte specific antinuclear antibodies. After proctocolectomy, the ANCA titres decreased in 10 patients, in two of whom they became negative. The titres remained the same in four patients with positive ANCA and increased twofold in one patient. Only one patient was proteinase-3 antibody positive and all 15 patients were myeloperoxidase antibody negative. The clinical condition improved in all patients, irrespective of the ANCA status after proctocolectomy. Seven patients, all of whom were positive for p-ANCA before proctocolectomy, had histological liver abnormalities. No correlation was observed between serum liver enzyme levels and ANCA staining patterns or titres. CONCLUSIONS: Proctocolectomy decreased the ANCA titres in the majority of our patients, suggesting that reduction of the inflammation or the available antigenic material modifies the immune disturbance related to ulcerative colitis.

Effect of cardiopulmonary resuscitation-induced stress on cell-mediated immunity.

Functions of cell-mediated immunity were studied from 11 patients after cardiovascular resuscitation and from matched controls who were simultaneously under observation. The resuscitated patients were anergic to recall skin antigens (93% negative) as compared to the controls (62%) (p less than 0.01). The anergic state correlated with the outcome of the patients. Lymphocyte numbers did not differ between these groups, but the number of T cells was significantly decreased, and B cells and granulocytes was increased in resuscitated patients. Lymphocytes from resuscitated patients responded to mitogenic stimulation although the responses were lower than those of the controls. Decreased lymphocyte responses were partly due to serum factor(s) which were not attributable to serum cortisol concentration. In addition the findings favour a change in the compartmentalization of lymphocyte subsets resulting in increased number of suppressor cells and/or increased sensitivity of lymphocytes to suppressive humoral factor(s) in the circulation. The anergy in skin evidently represents the final outcome of the dysfunction of several arms of cell mediated immunity.

Immune functions in Parkinson's disease lymphocyte subsets, concanavalin A-induced suppressor cell activity and in vitro immunoglobulin production.

Immune abnormalities, including the occurrence of autoantibodies against neural structures, diminished numbers of peripheral blood lymphocytes and reduced mitogen responses have been observed in patients with Parkinson's disease. In this study, we found that among the peripheral blood mononuclear cells (PBMNC) of patients with Parkinson's disease, there is a reduced number of cells spontaneously secreting immunoglobulins (Ig). After pokeweed mitogen stimulation, PBMNCs from patients with advanced Parkinson's disease had decreased capacity to elaborate Igs in vitro. In addition, there was evidence suggesting that OKT4+ (helper/inducer) subset may be decreased in Parkinson's disease along with disordered concanavalin A-induced suppressor cell activity. The findings do not primarily suggest an autoimmune pathogenesis of Parkinson's disease. The immune changes now observed partially resemble those seen in normal ageing, though being quantitatively exaggerated in Parkinson's disease. It is suggested that immune abnormalities in Parkinson's disease may result from disordered neural-immune regulation.

Circulating autoantibodies to a 240 kD fetal brain protein.

Antibodies (IgG and IgM) recognizing a 240 kD antigen of the cat fetal brain were found in sera of healthy people and in sera (IgG) obtained at uncomplicated delivery from the umbilical cord of the newborn infant. The method applied was immunoblotting. Using the same method, the 240 kD antigen could not be detected in the adult brain or other fetal tissues. It seems that the antigen is specific for the fetal brain. The role of the antigen and the origin of generation and significance of function of the antibodies in the circulation are the objects of our further studies.

PUVA treatment in chromium hypersensitivity: effect on skin reactivity and lymphocyte functions.

Two male patients with longstanding contact sensitivity to chromium were treated with PUVA. One patient, suffering from concomitant photosensitivity, reacted very favorably; his skin lesions cleared and light tolerance increased. This was paralleled by a decrease in the photopatch test reactivity and by the extinction of the patch-test reactivity on PUVA-exposed (pigmented) skin. Patch and photopatch tests on PUVA-shielded skin showed no decrease in skin test reactivity. PUVA-treatment caused a decrease in the number of rosette-forming T cells and an increase in lymphocyte stimulation in both patients. In one patient, abnormally high PHA-induced suppressor cell activities were recorded prior to treatment; after PUVA therapy the values were back to normal. In both patients, the PPD-induced suppressor cell activity of PWN response was clearly increased by PUVA-therapy. Other suppressor cell functions were not much affected. It is concluded that while PUVA-therapy may produce some systemic immunological effects, its abating effect on contact sensitivity and photosensitivity is mainly mediated through local mechanisms in the skin.

Cross-reactivity between antibodies to thyroid microsomal antigens and myeloperoxidase.

Antibodies against thyroid microsomal antigen (thyroid peroxidase, TMA/TPO) and myeloperoxidase (MPO) were measured from 115 patients with vasculitic disorders and 144 patients with suspected thyroid disorders. Nineteen patients, three with vasculitis and 16 with thyroid disorders, were shown to have both TPO and MPO antibodies, suggesting cross-reactivity of these antibodies. Their cross-reactivity was further strengthened by studying the capacity of antibodies to tolerate dilution in enzyme immunoassay and reactivity with synthetic TPO/MPO peptides.