BACKGROUND: We have previously reported an association between low IgA and allergic manifestations in early childhood (0-2 years) and have now followed our cohort for an additional 2 years. OBJECTIVE: To evaluate in a longitudinal community-based cohort study the association between maturation of Ig production and allergic manifestations in the first 4 years of life. METHODS: A cohort of 161 randomly selected children was followed from birth to the age of 42-48 months and evaluated at 18-23 months (EV1; n = 179) and again at the age of 42-48 months (EV2; n = 161). Diagnoses were made with the help of a clinical questionnaire, physical examination and skin prick tests (SPTs) to 10 common allergens. Serum immunoglobulins were measured at EV1 and EV2, and salivary IgA (sal-IgA) at EV2. RESULTS: Serum IgA, IgE, IgG1, IgG2 and IgG4 increased from 2 to 4 years of age (P
Respiratory tract infections, allergies and otitis media are common problems in early childhood. Our aim was to evaluate in a longitudinal community-based cohort study the association between maturation of immunoglobulin (Ig) and mannan-binding lectin (MBL) responses and disease manifestations in the first 4 years of life. Sustained low levels of IgA proved the strongest single indicator of susceptibility for recurrent otitis media (P = 0.008) and respiratory tract infections (P = 0.02), and this condition was also associated with low production of IgG subclasses. About 7% of the cohort had sustained low levels of MBL (
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
In this cross-sectional study a comparison was made of rheumatoid factor (RF) isotypes in 203 RF positive patients with arthritis. Of these, 129 had rheumatoid arthritis (RA) and 74 a milder disease that would formerly have been classified as probable RA. The majority (74%) of the RA patients had elevations of two or three RF isotypes compared with only 34% of the patients with the milder form of arthritis. A striking feature was that combined elevation of IgM RF and IgA RF was found in 67% of the RA patients compared to only 20% of the patients with milder arthritis who most frequently had an isolated elevation of IgM RF (41%). RA patients with an isolated elevation of IgA RF were younger and had a shorter disease history than RA patients with an isolated elevation in IgM RF or a combined elevation of IgA RF and IgM RF. The prevalence of raised IgM RF was, furthermore, found to increase with age and disease duration. We conclude that a raised level of IgA RF is an adverse phenomenon in patients with seropositive arthritis while patients with an isolated increase in IgM RF may be expected to experience a relatively mild disease course.
The diagnostic value of measuring rheumatoid factor (RF) by agglutination or isotype-specific enzyme-linked immunosorbent assay (ELISA) was compared. The study included 70 patients with rheumatoid arthritis (RA) and 205 patients with various other rheumatic conditions. Of the RA patients, 74% were RF-positive by agglutination and 90% had one or more RF isotypes elevated by ELISA compared to 14% and 22%, respectively, of the other patients. Strikingly, 70% of the RF-positive RA patients had an elevation of two or more RF isotypes compared to only 16% of the other RF-positive patients (P
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 ( 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.
We studied the relationship of serum levels of IgA and IgE to allergic manifestations and otitis media in a cohort of 179 Icelandic children, aged 18 to 23 months. Only one of the infants had IgA deficiency (less than 50 micrograms/ml); all the others had IgA levels that were normal for their age. The children were divided into three groups according to their IgA levels (lowest 25%, intermediate 50%, highest 25%) and the clinical findings analyzed accordingly. The cumulative incidence of definite allergic manifestations was 37%. Asthma and otitis media were significantly more common among the infants with low normal IgA levels than among those with intermediate to high IgA levels. There was also a significant association between the severity of allergic manifestations and low IgA levels (p = 0.002). Children with detectable IgE (greater than or equal to 0.23 kilounit/L) had a higher incidence of atopic manifestations than did children in whom IgE was not detectable, but only a weak correlation was found between the occurrence and extent of allergic symptoms and increasing amounts of IgE beyond the 0.23 kilounit/L level. These findings suggest that atopic manifestations in infants may be more dependent on delayed maturation of IgA production than on overproduction of IgE.
Eight patients with psoriatic arthritis entered an open study to determine the efficacy of oral cyclosporin A for their treatment. The starting dose was 3.5 mg/kg daily. Findings after the first six months are reported. One patient withdrew from the study after five months because of tremors, general malaise, and lack of improvement. Seven patients continued through the study, and marked improvement was found after two months in all clinical indices. The skin lesions improved in a parallel fashion. The cyclosporin A dose had to be reduced temporarily by 25% in three patients because of an increase in serum creatinine of more than 50%. A rise in diastolic blood pressure in three patients responded to treatment. The study suggests that cyclosporin A effectively treats arthritic manifestations of psoriasis as well as psoriatic skin lesions.
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.