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Biomedical subjects

E Soppi

Publications and source records attributed to E Soppi.

At least 37 records · Page 2Linked to original sources

Circulating myeloperoxidase may cause false negative findings in the analysis of myeloperoxidase antibodies in systemic vasculitis.

In systemic vasculitis reliable detection of myeloperoxidase antibodies (MPO-Abs) is of great clinical importance in the diagnosis and follow-up of patients. We have studied whether circulating myeloperoxidase (MPO) could have an effect on MPO-Ab findings. Serum MPO and MPO-Abs were measured in 50 healthy individuals, 35 patients and in the follow-up samples from two patients with Wegener's granulomatosis. Heating the sera at 56 degrees C for 30 min reduced the concentration of immunoreactive MPO both in control and patient sera. In 71% of the patient sera heating made initially negative MPO-Abs detectable. In a few cases with severe vasculitis the antibody findings remained totally negative. These results, together with the data from the follow-up samples from two patients with Wegener's granulomatosis, revealed that the serological diagnosis of vasculitis may be considerably delayed if only native samples are analysed for MPO-Abs. These findings are of considerable clinical significance for the interpretation of MPO-Ab results. Circulating myeloperoxidase affects MPO-Ab measurements, causing false negative findings in MPO-Ab assays. Therefore, it is recommended to denaturate circulating MPO by heating the sera before the analysis of MPO-Abs and to re-evaluate the cut off-values.

Adult↗

Lymphocyte response to cow's milk proteins in patients with cow's milk allergy: relationship to antigen exposure.

The cellular immune response to cow's milk was measured in patients with challenge-proven cow's milk allergy (CMA), manifested with either gastrointestinal or skin symptoms. After 2-4 weeks on milk elimination, 44 children, mean (SD) age 15.7 (9.4) months, were challenged, and cow's milk-induced lymphocyte transformation was measured before the clinical challenge (Day 1) and/or one week later (Day 8). During the clinical challenge period, 17 (39%) patients showed gastrointestinal reactions, 9 (20%) had urticarial or eczematous skin eruptions, and 18 (41%) were negative to challenge. On Day 1, the mean [95% confidence interval] stimulation index for lymphocytes in patients manifesting CMA with gastrointestinal symptoms, 2.60 [1.60, 4.10], was significantly higher than that in patients with skin symptoms, 1.15 [0.60, 2.30], or patients with negative clinical challenge, 0.83 [0.64, 1.08], F = 9.0, p = 0.001. After the clinical challenge (Day 8), this cow's milk-induced lymphocyte proliferation response was abrogated. At the same time, CMA patients evidenced a significantly higher spontaneous lymphocyte proliferation response in RPMI medium-containing control cultures than those with negative clinical challenge. We conclude that in patients with CMA, the number of circulating cow's milk-sensitized lymphocytes is depleted or their function is impaired after clinical exposure to cow's milk antigens.

Administration, Oral↗

Evidence for eosinophil activation in cow's milk allergy.

To assist in identifying pathogenetic mechanisms in different clinical manifestations of cow's milk allergy (CMA), the involvement of eosinophil cells in immunoinflammatory reactions was evaluated. The study population comprised 28 patients, aged from 5.8 to 43.0 months, who had challenge-proven CMA, manifested either cutaneously (n = 17) or gastrointestinally (n = 11). A clinical cow's milk challenge was performed in hospital after a 4 week cow's milk elimination period. Eosinophil activation in vivo was studied by measuring the serum level of eosinophil cationic protein (ECP) before the oral cow's milk challenge, mean (SD) 27 (12) hours after commencing the challenge and one week later. These results were compared to those of 80 non-allergic age-matched controls. During the challenge, the level of ECP increased from 6.2 (4.5, 8.0) micrograms/L to 20.0 (9.5, 30, 4) micrograms/L in CMA patients with skin manifestations but not in those with gastrointestinal symptoms. The increase was shown to be transient. We conclude that eosinophil degranulation is an important immunologic mechanism leading to allergic inflammation in cutaneously manifested CMA.

Blood Proteins↗

A prospective study of humoral immune responses to cow milk antigens in the first year of life.

Previous studies have shown that in cow milk allergy the specific immune response to dietary cow milk antigens is deficient. This study aimed at delineating the development of humoral immune response to cow milk antigens in healthy infants. Twenty-five healthy newborns were enrolled, and seen at scheduled visits at the ages of three, six and eleven months, and they formed two groups: those breastfed and those fed adapted cow milk formulae. The local immune response in the gut was approximated using the ELISPOT assay of circulating antibody secreting cells. At the age of three months, in the formula fed group, cells secreting specific IgA to cow milk antigens were detected despite low levels of IgA serum antibodies. The total number of IgA secreting cells increased with age (p = 0.001). The milk in the infant diet directly influenced this development so that the age related increase was significantly greater in the formula fed group (p = 0.04). The results indicate that diet has a significant effect on the developing immune system, and that healthy infants are able to respond in an antigen specific fashion to dietary antigens, which may be central in attaining clinical tolerance of such antigens.

Animals↗

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.

Adolescent↗

Production of immunoglobulin isotypes by peripheral blood mononuclear cells in multiple myeloma.

The immunoglobulin (Ig) isotype (IgG, IgA, IgM) production of peripheral blood mononuclear cells from 28 patients having multiple myeloma (MM) was analyzed. The total Ig secreting capacity of the cells, as measured by ELISA from the cell culture medium, was not found to be significantly reduced in MM (1,118 +/- 1,394 micrograms/l) as compared to the values of 9 controls (898 +/- 520 micrograms/l), but a significant isotype switching towards the tumor paraprotein type was observed in the patients with active MM (p < 0.001). The percentage of IgG in the active IgG-MM was 88 +/- 11% and that of IgA in the active IgA-MM 83 +/- 13%, the control values being 44 +/- 11% for IgG and 44 +/- 13% for IgA. The proportions of isotypes resembled those of the controls in the inactive phase of the disease. Despite this dominating paraprotein class isotype production, no evidence of Ig gene clonal rearrangements was found in cells studied by either Southern blotting or the more sensitive polymerase chain reaction method, which suggests that polyclonal rather than monoclonal PB B cells are responsible for the Ig production observed.

Adult↗

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.

Antibody Specificity↗

Familial scleroderma: HLA antigens and autoantibodies.

We report clinical and serological findings as well as the results of extended (HLA-A, B, C, DR and complotype) haplotype determinations of a family with two cases of systemic scleroderma and one case of primary biliary cirrhosis and incomplete CREST syndrome in a sibship of eight. In addition, one of these eight siblings has showed immunological findings of autoimmune disease for years but has not developed clinical symptoms. This family was studied by Soppi et al. in 1982; one member of the family has since then developed primary biliary cirrhosis and incomplete CREST type scleroderma. All family members with scleroderma or related disease as well as their sister with immunological abnormalities share the A2; B8; DR3 haplotype. Also some members of the family share the same haplotype but have remained healthy. This haplotype seems to be a predisposing factor but additional genetic or environmental factors are probably necessary for expression of autoimmune disease.

Adult↗

Essential cryofibrinogenaemia, leukocytoclastic vasculitis and chronic purpura.

Cryofibrinogenaemia refers to the presence of cold-precipitable proteins in plasma but not in serum. It is usually associated with malignancy, thromboembolic diseases or various inflammatory processes; rarely it may be essential. The most common clinical presentations of cryofibrinogenaemia are cold-intolerance, purpura, skin necrosis and ulcers. We describe a middle-aged woman with essential cryofibrinogenaemia, leukocytoclastic vasculitis, and chronic purpura for over 25 years with several exacerbations. In patients with otherwise unexplained purpura or skin necrosis, determination of plasma cryofibrinogen should be considered.

Adult↗

Immunologic disturbances in cow's milk allergy, 1: Delayed maturation of suppressor activity.

To assist in identifying pathogenetic mechanisms in different subtypes of cow's milk allergy (CMA), the function of immunoregulatory T-lymphocytes was studied. The study population consisted of 23 patients, mean [95% confidence interval] age of 25.6 [19.5, 33.6] months, who had challenge-proven cow's milk allergy manifested with either skin (n = 9) or gastrointestinal (n = 14) symptoms; in addition, 13 age-matched disease controls were studied. Patients with challenge-proven CMA were rechallenged to establish whether they had acquired clinical tolerance to cow's milk. The suppressor activity of isolated lymphocytes was measured in vitro by a cell coculture at rechallenge and in 10/23 patients at diagnosis. At diagnosis, patients with CMA (n = 10) showed a decreased mean [95% CI] suppressor activity, induced by either Concanavalin A, 7[-2,15]%, or cow's milk, 3[-8,14]% as compared with disease controls (n = 13), 19[15,24]% and 24[17,31]%; F = 7.1, p = 0.004 and F = 6.7, p = 0.005, respectively. At rechallenge the suppressor activity, induced both by Concanavalin A and cow's milk, reached the level of disease controls only in patients who had acquired clinical tolerance to cow's milk (n = 13/23), but not in those retaining CMA (n = 10/23). Our results indicate that the maturation of suppressor function is delayed in CMA, which might be of primary importance in the etiopathogenesis of CMA.

Child, Preschool↗

Immunologic disturbances in cow's milk allergy, 2: Evidence for defective interferon-gamma generation.

We have investigated the role of interferon-gamma (IFN-gamma) in the regulation of antigen-specific T-cell function in patients with cow's milk allergy. The study population consisted of 22 patients, aged from 7.6 to 56.9 months, who had challenge-proven cow's milk allergy (CMA) manifested with either skin (n = 9) or gastrointestinal (n = 13) symptoms. In addition, 11 age-matched children and 6 adults, mean (SD) age 31 (7) years, were studied as controls. Patients with challenge-proven CMA were rechallenged to establish whether they had acquired clinical tolerance to cow's milk. The spontaneous and mitogen-induced IFN-gamma and interleukin-4 (IL-4) generation of isolated lymphocytes was evaluated in vitro with commercial ELISA Kits at diagnosis and at reassessment. At diagnosis, the IFN-gamma production was not detectable in patients with CMA as compared with control children. IL-4 production was almost undetectable in all subjects in this study. However, at reassessment the CMA patients who had acquired clinical tolerance to cow's milk (n = 16) showed enhanced IFN-gamma production, when compared with that of control children, but still lower when compared with that of healthy adults. Our results indicate that the maturation of IFN-gamma producing T-cells is delayed in CMA, which could lead to a disturbance in the regulation of T-cell function. This defect might be an important etiologic factor for CMA.

Child, Preschool↗

Local immune response in patients with cow milk allergy: follow-up of patients retaining allergy or becoming tolerant.

To assist in identifying factors that determine the clinical outcome of cow milk allergy, we subjected to rechallenge 37 patients with a history of cow milk allergy, mean (+/- SD) age 27.6 +/- 7.1 months, after a follow-up of 13.5 +/- 5.1 months with a milk-free diet. A solid-phase enzyme-linked immunoassay was used to assess the total number of immunoglobulin-secreting and specific antibody-secreting cells among peripheral blood lymphocytes primed during provocation by milk antigens, giving indirect evidence of local immune response in the gut. Patients with persistent cow milk allergy (n = 13) had milder reactions at rechallenge than they had shown at the time of diagnosis. Numbers of immunoglobulin-secreting cells in these patients increased significantly from a geometric mean (95% confidence interval) in the IgA class of 1570 (1009, 2445) to 2984 (1941, 4583) IgA-secreting cells/10(6) cells, in the IgG class of 1445 (1067, 1959) to 2740 (1698, 4425) IgG-secreting cells/10(6) cells, and in the IgM class of 842 (534, 1325) to 2235 (1429, 3495) IgM-secreting cells/10(6) cells. By contrast, in patients (n = 24) who had acquired cow milk tolerance, the number of immunoglobulin-secreting cells did not increase during provocation. The total number of IgA-secreting cells before rechallenge was significantly higher than it had been before the initial challenge. The patients who acquired cow milk tolerance also had specific antibody-secreting cells of IgA isotype before the second challenge. These results indicate that in cow milk allergy the ability to mount a local immune response against cow milk antigens, particularly in the IgA class, is related to the suppression of clinical sensitivity.

Animals↗

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.

Antibodies, Antineutrophil Cytoplasmic↗