R. M. Valentijn

Presence of circulating macromolecular IgA in patients with hematuria due to primary IgA nephropathy

The relation between renal histologic features and the presence of circulating immune complexes was studied in 50 patients with hematuria. Primary IgA nephropathy was found in 25 patients, and various other forms of glomerulopathy were seen in the remaining 25 patients. Circulating immune complexes were detected with the 125I-C1q-binding assay, the conglutinin-binding assay, and the anti-IgA inhibition binding assay, the latter detecting specifically IgA-containing immune complex-like material. The 125I-C1q-binding assay gave negative findings for all patients except one. With the conglutinin-binding assay, immune complexes were found in a similar frequency for patients with and without IgA nephropathy. However, the anti-IgA inhibition binding assay gave positive results only in patients with primary IgA nephropathy (68 percent) and in none of the other patients. Sucrose density ultracentrifugation, as well as experiments in which the anti-IgA inhibition binding assay was performed with and without pretreatment of serum with polyethylene glycol, showed the presumed IgA immune complexes to have intermediate sedimentation coefficients (11 to 21S). The presence and level of this macromolecular IgA in the circulation correlated significantly (p less than 0.001) with the presence of hematuria in patients who had this clinical manifestation intermittently. Furthermore, a significant correlation (r = 0.69, p less than 0.0001) was found between the degree of hematuria and the degree of positive findings of the anti-IgA inhibition binding assay. This study shows that in patients presenting with hematuria, a positive finding on the anti-IgA inhibition binding assay is restricted to patients with primary IgA nephropathy and therefore could be of diagnostic value.

Monoclonal gammapathies in patients undergoing immunosuppressive treatment after renal transplantation

The frequency of monoclonal gammapathies (MG) and their possible origin were investigated in renal graft recipients undergoing immunosuppressive treatment. In a cross-sectional study, homogeneous immunoglobulins were found in 30% of the patients investigated. This incidence was 10-times higher than that in a control group of patients with chronic renal failure on dialysis treatment. The increase in the frequency of homogeneous immunoglobulins in the renal transplant recipients was related to the age of the patients but not to the duration of the immunosuppressive treatment. A longitudinal study in 55 patients demonstrated that most of the MG reflected transient B-cell monoclonal proliferations, probably due to an immunodeficiency; however, the incidence of benign and malignant B-cell neoplasias seemed also to be unusually high. These findings indicate that the immunosuppressive treatment enhances and accelerates an immunodeficiency which develops spontaneously with aging of the immune system; it also may contribute to the development of other age-related, both benign and malignant monoclonal B-cell proliferative disorders.

The clinical implications and the pathogenetic significance of circulating immune complexes in infective endocarditis

Circulating immune complexes were determined with the 125I-Clq binding assay and the conglutinin binding assay in a prospective, longitudinal study of 40 patients with infective endocarditis, 34 patients with endocardial defects and nonseptic fever and 25 patients with septicemia without endocarditis. Fourteen patients with uncomplicated valvular lesions constituted a control group. Upon admission, 63 percent of the patients with infective endocarditis had a positive 125I-Clq binding assay versus 9, 12 and 7 percent, respectively, of the other three groups (p less than 0.001). The incidence of positive conglutinin binding assays became significantly higher during the course of infective endocarditis (53 percent) than during the course of nonseptic fever (21 percent), but, upon admission, this difference was not significant. The high incidence of Clq-binding immune complexes among patients with infective endocarditis could be attributed mainly to those patients with the characteristic features of subacute endocarditis. The incidence of circulating immune complexes in acute endocarditis was low and did not contribute to making the clinically important distinction from septicemia without endocarditis. A rise in the 125I-Clq binding assay levels during the course of infective endocarditis correlated significantly (p less than 0.01) with failure of antibiotic treatment. With the 125I-Clq binding assay, significantly higher levels were found in patients with signs of renal involvement of cutaneous vasculitis than in patients without these extracardiac manifestations of endocarditis. These results show that the determination of circulating immune complexes has clinical implications for both the diagnosis and the management of infective endocarditis and that circulating immune complexes are probably involved in the development of glomerulonephritis and vasculitis.

The management of xerostomia in patients on haemodialysis: comparison of artificial saliva and chewing gum

Many patients on haemodialysis (HD) therapy suffer from a dry mouth and xerostomia. This can be relieved by mechanical and gustatory stimulation or palliative care. The aim of this crossover study was to investigate the effect and preferences of a sugar-free chewing gum (Freedent WhiteTM) and a xanthan gum-based artificial saliva (XialineTM) in the management of xerostomia in chronic HD patients. Sixty-five HD patients participated in a 6-week crossover trial. The artificial saliva was rated significantly lower than the chewing gum for effectiveness, taste and a global assessment. No preference differences were found for gender and age, although older subjects rated the artificial saliva with a higher mark. Thirty-nine subjects (60%) preferred chewing gum, 15% (n = 10) preferred the artificial saliva. Therefore, both chewing gum and artificial saliva could play an important role in the palliative care of xerostomia in HD patients.

Acute effects of hemodialysis on salivary flow rate and composition.

AIMS To evaluate acute effects of hemodialysis (HD) on the salivary flow rate, pH and biochemical composition before, during and after completion of a dialysis session. MATERIAL AND METHODS Unstimulated whole saliva (UWS) and chewing-stimulated whole saliva (CH-SWS) were collected in 94 HD patients. Salivary flow rate, pH, concentrations of total protein, albumin, cystatin C, secretory immunoglobulin A (S-IgA) and of sodium, potassium and urea were measured. RESULTS HD had an acute stimulating effect on the salivary flow rate (UWSbefore = 0.30+/-0.22 ml/min, UWSduring = 0.39+/-0.25 ml/min, p < 0.005). The mean pH of UWS showed a small but significant increase during HD mainly due to an increased watery secretion from the salivary glands. The salivary biochemical constituents changed markedly, but no significant difference in output was found. The electrolyte concentration did not change significantly during dialysis. The level of urea in CH-SWS declined to 40% (Ureabefore = 25.+/-6.4 mmol/l, Ureaduring = 15.3+/-4.5 mmol/1). CONCLUSIONS This study shows that HD has significant acute effects on both salivary secretion rate and protein concentrations in saliva. We conclude that the observed changes in salivary concentrations and proteins are mainly due to an increased watery secretion from the salivary glands.

Composition of IgA-Containing Circulating Immune Complexes in IgA Nephropathy

Macromolecular IgA is found with a relatively high frequency in the sera of patients with IgA nephropathy (IgAN). This macromolecular IgA consists of polymeric IgA, IgA-containing immune complexes, or both. The presence of polymeric IgA antibodies reflects a recent IgA response. Vaccination data in patients with IgAN suggest that these patients respond more vigorously with their mucosal immune system than do controls. The association of exacerbations with upper respiratory tract infections suggests that the immunogenic stimuli probably are of microbial origin and are presented to mucosal surfaces. Analysis by sucrose density ultracentrifugation has shown that the macromolecular IgA may contain IgG, IgA rheumatoid factor, and C3. The search for the antigen or antigens specifically responsible for IgAN has been unsuccessful. Although IgG and IgA rheumatoid factor may contribute, they do not account for the pathogenesis of the disease in all patients. Alternative mechanisms have to be assumed for patients who do not have detectable levels of IgA-containing immune complexes. They could have polymeric IgA or IgA-containing immune complexes intermittently, as has been shown in children with relapsing IgAN. The binding of circulating IgA antibodies to antigens present in the mesangium can lead to the local formation of deposits in the absence of circulating IgA complexes.

Immune complexes in leprosy patients from an endemic and a nonendemic area and a longitudinal study of the relationship between complement breakdown products and the clinical activity of erythema nodosum leprosum

Abstract The sera from 29 leprosy patients living in Surinam (endemic) and 41 leprosy patients living in The Netherlands (nonendemic) were tested for circulating immune complexes (CIC) with the C1q-binding assay and the conglutinin-binding assay and for complement levels including the breakdown product of C3 (C3d). In patients from the endemic area CIC were found with both assays throughout the entire leprosy spectrum. However, in untreated tuberculoid (T) and borderline tuberculoid (BT) leprosy patients from the nonendemic area, no CIC could be detected with either assay. These findings suggest that other factors in the endemic area, such as other tropical infections, might be responsible for the occurrence of CIC in these patients. In contrast, conglutinin-binding immune complexes were found in 10 out of 12 patients with T and BT leprosy who lived in the nonendemic area and received treatment. For 7 of these 10 patients only IgM was demonstrated in the CIC. The possible mechanisms involved in the appearance of conglutinin-binding immune complexes are discussed. Since CIC were found in patients with and without erythema nodosum leprosum (ENL), they were not specific for this disorder. Measurement of the C3d levels revealed a significant and specific correlation between elevated C3d levels and ENL (P