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Biomedical subjects

T Söderström

Publications and source records attributed to T Söderström.

10 recordsLinked to original sources

Immunoglobulin subclasses and prophylactic use of immunoglobulin in immunoglobulin G subclass deficiency.

Persistent low serum levels of one or several immunoglobulin G (IgG) subclasses can be found in a high proportion of adult patients with increased susceptibility to infections. It is hard to envision that the low subclass level in itself is responsible for this susceptibility because healthy blood donors have been described who are completely devoid of certain subclasses in serum. This apparent discrepancy may be partly explained by the observation that most subclass-deficient patients have underlying aberrations in T-cell and B-cell interaction and function that may impair their capacity to compensate for even minor deficiencies. A prospective blind crossover study of the effect of prophylactic Ig substitution therapy was done in 43 adult patients with IgG subclass deficiency. The patients were randomized to receive 1 year of therapy with intramuscular Ig 25 mg/kg/wk or 1 year of saline injections. A significant protective effect of the prophylactic Ig therapy was seen with a great reduction in the number of days of infection. In addition, several immunologic parameters were altered after 1 year of Ig therapy. Nineteen of the patients later were included in an open study using 50 mg/kg/wk of Ig. After 6 months of treatment, significant protection against infection was observed, with a reduction of 6.2 days in the number of days per month with infection. This marked effect of prophylactic Ig suggests that the Ig aberrations seen in IgG subclass-deficient patients contributed to their susceptibility to infection. The effect of 25 mg/kg/wk was much less pronounced than that of 50 mg/kg/wk, and normal serum IgG subclass levels were not achieved even during the higher-dose therapy. However, it seems likely that subcutaneous or intravenous administration of larger doses of Ig would allow for more efficient therapy.

Adult

IgG subclass deficiency with or without IgA deficiency.

IgG subclass deficiency (IgGSD) is difficult to define since reference materials vary between laboratories and the clinically relevant cut off levels for the various subclasses are not well known. The diagnosis of IgGSD should be based on more than one determination since the levels vary, due to various factors such as infections, operations, etc. There is a relation between IgGSD and occurrence of frequent infections, but at the same time even total lack of a subclass can be seen in healthy individuals. Infections in the upper and lower respiratory tract predominate. Gm allotypes influence IgG subclass levels. Most IgGSD patients are homozygous in the Gm system. Immunocytes producing IgG3 in the nasal mucosa correlate with serum IgG3 levels, whereas rectal IgG1 producing cells relate to serum IgG1 levels. This may reflect differences in antigen and/or mitogen exposure at the two mucosal sites. IgG2SD is the predominant form of IgGSD among children, whereas after puberty IgG3SD is most common. At the same age period there is a switch in sex distribution from three boys/one girl to one male/three females. Various abnormalities in B and T lymphocyte numbers and function are often found. In a double blind crossover study of Ig prophylaxis over 2 years in 43 IgGSD adult patients a significant decrease in the number of days with infections was seen both in the whole group and among the IgG1 deficient. Days with bronchial constriction were also significantly decreased among the 22 patients who had asthma as well. Acute bronchitis became significantly less frequent in the IgG3 deficient patients during Ig prophylaxis. This was seen in those under the lower range of 0.41 g/liter of Oxelius' early normal material, although many recent reference materials suggest 0.14-0.15 g/liter of IgG3 as the cut off. In a group of 25 consecutive patients with IgGSD + IgA deficiency recurrent respiratory infections were the major problem and lung function impairment was found in 12, and bronchiectasies in 5. Still many individuals with this combined deficiency have been reported to be healthy, again illustrating our limited understanding of these conditions.

Disease

An immunological study in patients with seborrhoeic dermatitis.

The humoral and cellular immune-status was studied in 30 patients with seborrhoeic dermatitis. Increased frequencies of natural killer cells were found in 46% of patients. Furthermore, subnormal mitogen stimulation responses were demonstrated in 13 patients, whereas two individuals were found to have very high numbers of activated T lymphocytes in peripheral blood. Higher-than-normal total serum IgG and IgA was observed in 14 and 11 patients, respectively. For nine of 12 patients with skin lesions, dermal perivascular cell infiltrates were seen. The majority of the infiltrating cells reacted with anti-CD4 antibodies. HLA-DR-expressing keratinocytes were found in two biopsies. The study suggests that patients with seborrhoeic dermatitis may have depressed T-cell function. This could have a bearing on their susceptibility to the Pityrosporum ovale-associated dermatitis. The very high frequencies of activated T cells observed in the peripheral blood of two otherwise healthy seborrhoeic individuals suggests that intermittent systemic immune activation may occur. Seborrhoeic dermatitis is a common skin disease. It can be diagnosed by its characteristic red to yellow-brown lesions covered with greasy scales distributed in areas with a high number of sebaceous glands, such as the scalp, face and upper trunk. There is an association between seborrhoeic dermatitis and the lipophilic yeast Pityrosporum ovale but its exact aetiological role is not known. The yeast is a member of the normal cutaneous flora but also the aetiological agent of pityriasis versicolor and Pityrosporum folliculitis. P. ovale can activate complement via the direct and alternative pathways. This may play some part in the induction of inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The evaluation of various methods and antigens for the detection of antibodies against Pityrosporum ovale in patients with seborrhoeic dermatitis.

Sera from 10 patients with seborrhoeic dermatitis and from 10 age-matched healthy individuals were examined for IgG activity against Pityrosporum ovale. The IgG activity was analysed using the following techniques: an enzyme-linked immunosorbent assay (ELISA) against whole P. ovale cells, purified cell-wall carbohydrate or protein extract, an indirect slide-immunofluorescence assay and fluorescence-activated flow cytometry using the whole organism as antigen. The ELISA method using the protein antigen was the only technique that showed a significant difference between patients and controls; a lower antibody response was found in the seborrhoeic dermatitis patients compared to healthy controls.

Adult

Isotype distribution of mucosal IgG-producing cells in patients with various IgG subclass deficiencies.

The subclass distribution of IgG-producing immunocytes was examined by immunohistochemistry in nasal and rectal mucosa of infection-prone patients with untreated IgG subclass deficiencies. Biopsy specimens from the two sites were obtained in 18 clinically and serologically well-characterized adult subjects; only a nasal or rectal sample was available from nine similar patients. Chronic lung disease was common in the patient groups with selective serum IgG1 deficiency and combined IgG1 and IgG3 deficiency, whereas the other categories of patients had mainly upper airway and other mild infections. Serum IgG2 or IgG3 deficiency was usually expressed also at the cellular level in rectal mucosa, and the proportion of rectal IgG1 cells was significantly correlated with the IgG1 level (r = 0.90, P less than 0.001). Likewise, there tended to be a decreased expression of the actual subclass at the cellular level in nasal mucosa of patients with serum IgG1 or IgG2 deficiency. Conversely, the median nasal proportion of IgG3 cells was remarkably unaffected by a deficiency of this subclass in serum and rectal mucosa. Interestingly, these patients rather tended to have raised IgG3 and reduced IgG2 cell proportions in their nasal mucosa, although this apparent local IgG3 compensation was nevertheless strongly correlated with the serum IgG3 level (r = 0.87, P less than 0.002). These disparities may reflect different antigenic and mitogenic exposure of the two tissue sites; for example, a persistent protein bombardment of the nasal mucosa that could conceivably override locally a B cell maturation defect. The possible clinical consequences of such variable mucosal expression of IgG subclass deficiencies remain to be studied.

Adult

Opinions on treatment of women with habitual abortion based on investigations for blocking antibody and autoantibodies.

Three hundred and thirty-seven women with habitual abortion of unknown etiology were studied for cellular reactivity and blocking antibody in one-way mixed lymphocyte culture. Their sera were investigated for anti-cardiolipin antibodies, antinuclear antibodies, and antibodies against DNA, and the activated partial thromboplastin time (APTT) and complement levels of their plasma were determined. Increased anti-cardiolipin antibody levels were demonstrated in 77 (22%) of the 337 women, all of whom were considered healthy and had no signs of autoimmune disease. Most patients with high anti-cardiolipin antibody levels displayed lowered values of complement factor C4. According to our experiences, the mere occurrence of anti-cardiolipin antibody in women with habitual abortion is no absolute cause for treatment with prednisolone, not even in cases with greatly elevated anti-cardiolipin values. Therapy with prednisolone and acethylsalicylic acid (ASA) during pregnancy should be given to those women who have high levels of anti-cardiolipin antibodies concomitant with high APTT values, low values of complement C4, and strong blocking antibody. Anti-cardiolipin antibody has been investigated during pregnancy in 136 normal pregnant women, 11 of whom (8%) were positive at any sampling occasion, but only one of whom (1%) had high levels. Evidently the development of anti-cardiolipin antibody is no normal feature of pregnancy among Swedish women and thus the high frequency found among healthy Swedish women with habitual abortion remains unexplained. We have introduced an immunization program of leukocyte transfusions in habitual abortion. The development of previously absent blocking antibody seems to be a valuable prognostic sign of possible success for immunization therapy against habitual abortion.

Abortion, Habitual

Immunoglobulin and complement studies in children with Schönlein-Henoch Syndrome and other vasculitic diseases.

In 35 children with Schönlein-Henoch Syndrome (SHS) serum IgG, IgM, and IgA concentrations were increased in 15%, 21%, and 44% of cases, respectively. Seven children with other vasculitic syndromes (VS) had normal serum Ig concentrations. Serum concentration of IgG subclass IgG1 was increased in 72% of children with SHS and 57% with VS. In SHS this was related to the presence of arthritis, but inversely related to nephritic symptoms. Only a few children had IgG subclasses IgG2, IgG3, or IgG4 concentrations outside the normal ranges. Platelet associated Ig (PAIg) was found in 75% of children with SHS or VS. In SHS the identification of increased amounts of PAIgG was related to the presence of nephritis. The serum concentration of properdin, a component of the alternative complement system, was reduced in 21% of children with SHS. This was related to the presence of abdominal symptoms or nephritis. No cases of retinal vasculitis was observed, but 4 of 22 children with SHS had punctuate retinal haemorrhages. SHS and VS may be clinical variations of the same syndrome. The immunological aspects indicate a close relationship with autoimmune diseases.

Adolescent

Polymorphonuclear leucocyte function during pregnancy.

Polymorphonuclear leucocyte (PMN) function was studied in pregnant women and related to the serum concentration of pregnancy zone protein (PZP) and to mixed lymphocyte culture (MLC) reactivity. Neutrophil chemotaxis was depressed in pregnant women. Pregnancy serum inhibited the MLC-reaction. The serum levels of PZP were inversely related to chemotactic responsiveness (P less than 0.05) and depression of MLC reactivity (P less than 0.01). The capacity to reduce nitroblue tetrazolium was depressed in PMNs from pregnant women, and pregnancy serum inhibited phagocytosis of Escherichia coli by control PMNs. Neutrophils from pregnant women showed increased chemiluminescence during phagocytosis of zymosan. The results may be explained by depression of ingestion by pregnancy serum and increased oxidative metabolism in PMNs from pregnant women.

Chemotaxis, Leukocyte