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Biomedical subjects

H Valdimarsson

Publications and source records attributed to H Valdimarsson.

At least 55 records · Page 3Linked to original sources
PubMed1995

Psoriasis: a T-cell-mediated autoimmune disease induced by streptococcal superantigens?

Psoriasis is a T-cell-mediated disease that can be triggered by infection with group A beta-haemolytic streptococci. It is proposed that psoriatic skin lesions are initiated by exotoxin-activated T cells, and persist because of specific T cells that react both with streptococcal M protein and a skin determinant, possibly a variant of keratin. As discussed here by Helgi Valdimarsson and colleagues, cytokines released by the superantigen (SAg)-stimulated T cells could induce or enhance the expression of the crossreactive autoantigen, leading to the rescue and activation of autoreactive T cells. In this way, the SAg-determined T-cell receptor V beta phenotype would be maintained by T cells in psoriatic lesions.

Autoimmune Diseases↗
PubMed1995

Clinical implications of IgA rheumatoid factor subclasses.

OBJECTIVES: To evaluate the diagnostic and pathogenetic significance of IgA rheumatoid factor (RF) subclasses in rheumatoid arthritis (RA). METHODS: Rheumatoid factors of the IgA class and IgA1 and IgA2 subclasses were measured by enzyme linked immunosorbent assay in 58 patients with RA, 31 patients with other rheumatic diseases, 30 non-rheumatic individuals with increased concentrations of IgA RF, and in 100 randomly selected healthy controls. RESULTS: Using a 95% cut off for the controls, 55% of the RA patients had increased total IgA RF, 64% IgA1 RF, and 60% IgA2 RF. RA patients with extraarticular manifestations more often had increased concentrations of IgA RF and both subclasses than patients without such manifestations (p < or = 0.01). Nearly all (31/32) RA patients with increased IgA RF had increases in both IgA RF subclasses, compared with 67% (20/30 of nonrheumatic symptom free individuals with increased IgA RF (p = 0.002). CONCLUSION: Increased concentrations of the IgA2 RF subclass appears to be more specific for RA than increased IgA1 RF. Measurement of IgA RF subclasses may be clinically useful.

Arthritis, Rheumatoid↗
PubMed1995

Selective increase of IgA rheumatoid factor in patients with gluten sensitivity.

An increased prevalence of raised autoantibodies, including rheumatoid factor, has been reported in patients with gluten sensitivity. However, rheumatoid factor has only been measured in small groups of patients and the findings have been conflicting. In this study IgM, IgG and IgA rheumatoid factor was measured in 89 patients with dermatitis herpetiformis and 22 patients with coeliac disease and compared with 89 normal controls. There was an increased prevalence of elevated IgA rheumatoid factor in the patients with dermatitis herpetiformis (13.5%; p = 0.036) and coeliac disease (18.2%; p = 0.078), while no such increase was found for the IgM or IgG rheumatoid factor isotypes. This selective increase of IgA rheumatoid factor suggests that rheumatoid factor production in patients with gluten sensitivity primarily results from immunological activation in the gut mucosa.

Adult↗
PubMed1995

Raised IgA rheumatoid factor (RF) but not IgM RF or IgG RF is associated with extra-articular manifestations in rheumatoid arthritis.

In rheumatoid arthritis (RA) seropositivity has been associated with poor prognosis including bone erosions and extra-articular manifestations. However, findings have been conflicting on the association between individual rheumatoid factor (RF) isotypes and extra-articular manifestations. In this study the occurrence of extra-articular manifestations was examined in the context of the RF isotype patterns rather than individual RF isotypes. IgM, IgG and IgA RF was measured by ELISA in 74 patients with RA and the findings correlated with the presence or absence of extra-articular manifestations. Of the IgA RF positive patients 80% had one or more extra-articular manifestations. In contrast, only 21% of patients with raised IgM and/or IgG RF but normal IgA RF had some extra-articular manifestations and 27% of the seronegative patients. It is concluded that the previously reported association between raised RF and extra-articular manifestations in RA can largely be attributed to the IgA RF isotype.

Adult↗
PubMed1994

Opsonization and antibodies to capsular and cell wall polysaccharides of Streptococcus pneumoniae.

Opsonin-dependent phagocytosis is believed to be the major defense mechanism against Streptococcus pneumoniae. In addition to type-specific antibodies to pneumococcal capsular polysaccharides (PPS), most persons also produce antibodies to cell wall polysaccharide (CWPS), which may be detected in antibody assays due to contamination of PPS antigens. Antibodies to CWPS and PPS from common serotypes were analyzed in relation to opsonic activity before and after vaccination of healthy adults. A highly significant relationship was generally found between opsonization and pneumococcal antibody levels, and this correlation increased markedly by neutralization of CWPS antibodies. This applied in particular for IgG2, which showed no correlation without neutralization. Adsorption of PPS antibodies almost abolished the opsonic activity, whereas removal of CWPS antibodies had no effect. These findings indicate that opsonization of pneumococci is almost exclusively mediated by PPS antibodies and emphasize the importance of neutralizing CWPS antibodies when immunity to this organism is evaluated.

Adult↗
PubMed1994

Cord blood IgE levels are influenced by gestational age but do not predict allergic manifestations in infants.

The predictive value of cord blood IgE (cIgE) for atopy and related disorders was investigated. Samples were collected from 792 infants delivered consecutively at the National University Hospital in Reykjavík in 1987. The concentration of IgE, but not that of IgA, was found to increase with increasing gestational age at birth. There was no correlation between IgE and IgA levels in individual samples. At the age of 18-23 months 180 of these children were studied for manifestations of allergy and related disorders. Included were all available infants with detectable (> or = 0.23 kU/L) cIgE. However, infants born by Cesarean section or with IgA exceeding 10 mg/L were excluded because of potential contamination with maternal blood. The clinical evaluation was made without knowledge of the IgE levels. Sixty-six of the 180 participants (36.6%) were judged to have had definite allergic manifestations. However, no striking correlation was found between allergic symptoms and cIgE levels in this study, nor did high levels of IgE add significantly to the predictive value of family history. Children with atopic features had more frequently been affected by otitis media. Unexpectedly, infants with intermediate cIgE levels (0.2-0.6 kU/L) were significantly less affected by otitis media than children with unmeasurable (< 0.2 kU/L) or high (> or = 0.7 kU/L) cIgE levels. It is concluded that cord blood IgE can not be used to predict allergic manifestations in children under the age of 2 years.

Breast Feeding↗
PubMed1994

Decreased T cell reactivity to trypsinized group A, type M22 streptococci in psoriasis.

The proliferative responses of peripheral blood mononuclear cells from patients with guttate and chronic plaque psoriasis to streptococcal M protein were investigated using whole and trypsinized group A M22-positive streptococci. Peripheral blood mononuclear cell responses to whole type M22 group A streptococci were significantly increased in guttate, but not chronic plaque, psoriasis patients compared to 17 non-psoriatic controls (p < 0.05; n = 17). A significant reduction of this response was observed in both guttate (p < 0.001; n = 17) and chronic plaque (p < 0.01; n = 27) psoriatic patients, but not in the control group, after repeated trypsinization to remove M protein from the streptococci. Furthermore, the difference between the peripheral blood mononuclear cell response to untrypsinized and trypsinized streptococci was significantly greater in the guttate patients than in the controls (p < 0.02). This preliminary study has shown an increased reactivity of T lymphocytes with specificity for trypsin-sensitive protein expressed by type M22 streptococci in the peripheral blood of patients with psoriasis.

Adolescent↗
PubMed1993

Splenic uptake of immune complexes in man is complement-dependent.

We have examined the effects of hereditary homozygous C2 deficiency on the processing of radiolabeled soluble immune complexes (IC). A patient with C2 deficiency was studied before and after treatment with fresh frozen plasma (FFP). Hepatitis B surface Ag (HBsAg):anti-HBsAg immune complexes were prepared in vitro using Ag radiolabeled with 123I, and injected intravenously. Dynamic and static gamma-scintigraphy was performed to delineate the sites and kinetics of complex clearance. The patient was initially studied when her C2 level and CH50 were zero, and again 1 wk later after treatment with 12 units of FFP, which normalized these parameters. Before treatment there was rapid uptake of complexes by the liver (t90% [time for 90% uptake] = 13.6 min) and rapid clearance from the circulation (t1/2 = 6.8 min). No splenic uptake was detected, and there was no binding of complexes to erythrocyte CR1. Between 30 and 60 min there was release of 11% of the tracer from the liver. In the second study, performed after normalization of classical pathway complement activity, the t1/2 of IC clearance increased to 9.8 min, and t90% was 27 min. Twenty percent of injected complexes now localized to the spleen, and there was no longer any release of complexes between 30 and 60 min. The kinetics of IC processing and the sites of uptake in this posttherapy study were closely similar to two normal subjects studied in parallel, with a maximum of 72% of injected complexes binding to erythrocytes. These observations indicate that the uptake of immune complexes in the spleen in humans is complement-dependent, and suggest that the observed predisposition to SLE in patients with complement deficiency may be related to abnormal processing of immune complexes.

Antigen-Antibody Complex↗
PubMed1993

Group A streptococcal antigen-specific T lymphocytes in guttate psoriatic lesions.

A strong association exists between guttate psoriasis and group A, beta-haemolytic streptococcal infections. To demonstrate the presence of streptococcal-specific T cells in psoriatic skin, T-cell lines (TLs) were established from biopsies of lesions from five patients with guttate psoriasis, and compared with TLs from five patients with eczema, five with lichen planus, two with pityriasis rosea and three with nickel contact dermatitis. TLs from purified protein derivative (PPD)-induced delayed hypersensitivity sites in three normal individuals were also studied. All five of the psoriatic TLs responded in a proliferation assay to heat-killed isolates of group A streptococci, compared with only one eczema, two lichen planus and one pityriasis rosea. The response of one nickel contact dermatitis and two PPD TLs to group A streptococci was markedly less than to nickel and PPD, respectively. One of the psoriatic TLs was cloned in the presence of type 5 streptococcal M protein. The nine clones obtained were all CD3+, CD4+, CD45RO+, TCR alpha, beta+, gamma, delta-. However, they were all unreactive with antibodies to TCR V beta 5, 6, 8 or 12. Eight of the nine clones reacted, to a varying extent, to one or two of three preparations of group A streptococci expressing different M proteins. The streptococcal response of four consistently reactive clones from this patient was HLA-DR-restricted and inhibited by anti-HLA-DR antibody in a dose-dependent manner. On stimulation these four clones secreted high levels of gamma-interferon and detectable levels of IL-2, IL-10 and granulocyte/macrophage colony stimulating factor (GM-CSF) depending upon the nature of the stimulus, but no IL-4 or TNF-alpha production was detected. This study has demonstrated, for the first time, that T lymphocytes specific for group A streptococcal antigens can be consistently isolated from guttate psoriatic lesions. The role of streptococcal-specific T cells in the pathogenesis of psoriasis remains to be determined.

Antigens, Bacterial↗
PubMed1993

Restricted T-cell receptor V beta gene usage in the skin of patients with guttate and chronic plaque psoriasis.

A strong association between acute guttate psoriasis and group A, beta-haemolytic streptococcal infections is well established. Furthermore, streptococcal M proteins and toxins have been shown to act as superantigens, stimulating subpopulations of T lymphocytes expressing particular V beta families. We have therefore studied the possible role of streptococcal superantigens in psoriasis by staining peripheral T lymphocytes and skin sections from patients with guttate or chronic plaque psoriasis for the expression of nine TCR V beta families, using a range of monoclonal antibodies. A marked over-representation of V beta 2+ T lymphocytes was observed in the dermis and epidermis of patients in both groups, when compared with T lymphocytes in their peripheral blood. A less marked dermal increase in V beta 5.1+ T lymphocytes was also observed in these patients. These findings are consistent with the involvement of a superantigen, possibly streptococcal, in the pathogenesis of psoriasis.

Acute Disease↗
PubMed1993

The role of cytokines in the generation of skin lesions in dermatitis herpetiformis.

The infiltration of polymorphonuclear neutrophils (PMN) into the upper dermis which characterizes the skin lesions of dermatitis herpetiformis (DH) has never been satisfactorily explained. This study has shown that lesional skin of patients with DH has increased expression of endothelial leucocyte adhesion molecules (ELAM) in the deep dermis, combined with a markedly increased staining for interleukin 8 (IL-8) in the basal epidermal layer. Dendritic cells which stained for granulocyte macrophage colony stimulating factor (GM-CSF) were also observed at the dermo-epidermal junction, and this phenomenon was more pronounced in lesional than in uninvolved DH skin. ELAM, IL-8 and GM-CSF are known to promote infiltration and activation of PMN, and it is suggested that these cytokines may play a key role in the generation of DH lesions.

Adult↗
PubMed1993

Renal function and biopsy findings after 5 years' treatment with low-dose cyclosporin for psoriasis.

Renal biopsies were performed in eight patients with chronic plaque psoriasis who had been treated with low-dose cyclosporin (CyA) (range 1-6 mg/kg/day; average dose 3.3 mg/kg/day) for an average period of 5 years. In six of the eight patients biopsies showed features consistent with CyA nephrotoxicity. Tubular atrophy and arteriolar hyalinosis were present in all six, four had an increase in interstitium, and two showed an increased incidence of glomerular obsolescence. Two of the patients showed all of these features, two patients had three features, and the remaining patients had two features. Renal function was assessed by glomerular filtration rate (GFR) and serum creatinine. Both a fall in the GFR and a rise in the serum creatinine correlated with the severity of the features of CyA nephrotoxicity seen on biopsy. However, the best predictor of the biopsy findings was a failure of renal function to show significant improvement when CyA was discontinued for a month. CyA has been discontinued in two of the eight patients who had the most severe features of CyA nephrotoxicity on renal biopsy. In both patients there has been improvement of renal function after 1 year of follow-up.

Adult↗
PubMed1993

Dermatitis herpetiformis--an autoimmune disease due to cross-reaction between dietary glutenin and dermal elastin?

Dermatitis herpetiformis (DH), is associated with skin eruptions and granular depositions of IgA in the papillary dermis, but this is not a feature of coeliac disease (CD). The specificity of the IgA in the skin is unknown. High molecular weight glutenin (HMW-g), a component of gluten, has been shown to have structural similarities to human elastin. This paper reports immunoadsorption studies which suggest that human serum may contain antibodies which cross-react with HMW-g and elastin. DH patients had significantly lower levels of IgA antibodies to HMW-g and to elastin than both CD patients and healthy controls. Furthermore, introduction of a gluten-free diet (GFD) was associated with a further reduction in the amount of IgA antibodies to elastin in the DH patients. This diet-associated decrease of elastin antibodies was restricted to the IgA isotype. A significant correlation was observed between IgA antibodies to HMW-g and elastin in healthy controls and CD patients, while no such correlation was found in patients with DH. These findings could indicate that HMW-g induces production of antibodies to elastin, which are deposited in the skin, and that when the antigenic stimulus is removed, these antibodies are further reduced due to continuous dermal deposition. It is postulated that DH may be an autoimmune disease due to cross-reactivity between dietary glutenin and dermal elastin.

Adult↗
PubMed1993

Normal response to tumor necrosis factor-alpha and transforming growth factor-beta by keratinocytes in psoriasis.

Normal and chronic plaque psoriatic keratinocyte cultures were tested for their in vitro response to 2-200 ng/ml TNF-alpha and 0.1-10 ng/ml TGF-beta in a serum-free culture system. All normal and lesional psoriatic epidermal cell cultures showed a dose- and time-dependent inhibition of growth in response to TNF-alpha and TGF-beta. Inhibition in individual cultures was first seen at a concentration of 2 ng/ml for TNF-alpha and 0.1 ng/ml for TGF-beta at day 2, but became significant at 20 ng/ml and 1 ng/ml for TNF-alpha and TGF-beta respectively at days 2-6. This effect was statistically significant at days 3-4 for the group of normal (TNF-alpha and TGF-beta, n = 10, p < 0.01) and psoriatic cultures (TNF-alpha, n = 9, p < 0.01; TGF-beta, n = 7, p < 0.05). Epidermal cells from normal and psoriatic skin were inhibited to the same extent at the same optimal concentrations by each cytokine. Inhibition was abolished by the addition of specific antibody to each cytokine, whilst antibody to a different cytokine had no effect. Nuclear and/or nuclear membrane staining was observed with antibody to the p55 TNF receptor both in cultured keratinocytes and in the upper epidermal layers of both normal and psoriatic skin. In contrast, plasma membrane and cytoplasmic expression of the p55 TNF receptor was observed on macrophages and lymphocytes infiltrating psoriatic dermis. This study has shown that the growth of normal and psoriatic keratinocytes was equally inhibited by TNF-alpha and TGF-beta in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Reciprocal changes in complement activity and immune-complex levels during plasma infusion in a C2-deficient SLE patient.

Although systemic lupus erythematosus (SLE) is abnormally common in individuals with complement deficiency, conclusive evidence has been lacking for a direct causal relationship between disease manifestations and a missing complement component. A patient with C2 deficiency and SLE has been treated with 56 courses of fresh frozen plasma (FFP) infusions over a period of 8 years. Each infusion, involving a total of 12 units of FFP administered in equal doses over 4 consecutive days, has consistently resulted in a transient restoration of the classical pathway of complement, and a full clinical remission lasting 6-8 weeks. This report is concerned with changes in the levels of immune complexes, C2 and C3d during an infusion cycle. Four progressively rising peaks in C2 and C3d were observed during the 4 days of the plasma infusion, and these peaks coincided with four reciprocally descending troughs in the levels of immune complexes. Identical fluctuations have been consistent in all the plasma-infusion cycles that have so far been monitored, and their consistent association with clinical remissions indicates a causal relationship between the C2 restoration and clinical remissions in this C2-deficient SLE patient.

Antigen-Antibody Complex↗