Monoclonal immunoglobulins in patients with renal transplants: characterization, evolution and risk factors.

Gammopathies were found to be present in 25 (13%) of 192 HIV-negative renal transplant recipients with more than 30 months follow-up prospectively investigated for monoclonal or oligoclonal immunoglobulins (mIg) by agarose gel electrophoresis and immunofixation. Eleven patients had only one monoclonal band, whereas 14 had two or more bands. Of these bands, 60% were IgG kappa, 29% IgG lambda and 11% IgM lambda or kappa, and 90% did not exceed 2 g/l. Most gammopathies occurred early post-transplant (median 5 months) and they were always transient. Some predisposing factors for mIg emergence could be identified: 1. age, but only in women, 2. duration of dialysis, 3. occurrence of prior cytomegalovirus infection, and 4. immunosuppressive regimen including cyclosporine. Serological evidence for active EBV infection was obtained in ten patients, but in six cases infection occurred subsequent to the finding of mIg. In eight patients, the clinical course was characterised by severe infection or tumours (one Kaposi's sarcoma, one B-cell brain lymphoma). The present findings and experimental studies support the view that the development of mIg in renal transplant patients is associated with a failure of regulatory T-cell function. This T-B-cell imbalance requires a careful follow-up in these patients.

[Monoclonal immunoglobulins in kidney transplantation. Characterisation, evolution and risk factors]. / Immunoglobulines monoclonales en transplantation rénale. Caractérisation, évolution et facteurs de risque.

Sera from 192 consecutive HIV negative renal transplant patients with more than 6 months follow-up were investigated for monoclonal or oligoclonal immunoglobulins (mIg) by immunoelectrophoresis or immunofixation. Gammapathy was present in 25 patients (13 percent). Eleven patients had only one monoclonal band, whereas 14 had two or more bands. Sixty percent were IgG K, 29 percent IgG lambda and 11 percent IgM lambda or K. Ninety percent of these mIg did not exceed 2 g/l; mIg appeared within 2-27 months following the transplantation (mean time-lag 8 +/- 6.4 months). The mIg were often transient: 20 disappeared within 1-33 months, most of them (14) being absent after 1 year of follow-up. Some risk factors for mIg could be identified: the patient's age (a risk factor only in women); the duration of dialysis; the occurrence of prior CMV infection; treatment with cyclosporine. The persistence of mIg was characterised by one or more of the followings: high titer of mIg, EBV infection or reactivation, inability to switch from IgM to IgG CMV antibodies. No significant association was found with the hepatitis B surface antigenemia, previous infection with hepatitis C or the number of rejection episodes. In 6 patients, the clinical course was characterised by severe infection or tumours. Although long-term follow ups are not yet available, patients in whom one or more mIg have been demonstrated should be carefully followed.

[Silent myocardial ischemia during hemodialysis in patients with chronic renal insufficiency]. / L'ischémie myocardique silencieuse au cours de l'hémodialyse des insuffisants rénaux chroniques.

A prospective search for episodes of silent myocardial ischaemia (SMI) was carried out during sessions of haemodialysis in 62 patients with chronic renal failure and was positive in 37.1% of the cases. The occurrence of SMI is correlated with the number of cardiovascular risk factors (p = 0.008) and particularly with diabetes (p = 0.012), smoking (p = 0.007) and age (p = 0.02), as well as with the type of nephropathy that had caused the renal failure (p = 0.02). During a 6-month follow-up two patients died; both had silent myocardial ischaemia on Holter recordings. In these anaemic patients, haemodialysis might sensitize the detection of ischaemia by the concomitant occurrence of hypotensive, hypovolaemic or hypoxic episodes, thus playing a aggravating role. The existence of such episodes characterizes a subgroup of patients at high cardiovascular risk for whom the prognosis and the best therapeutic approach remain to be determined.

[Frequency of painless myocardial ischemia during hemodialysis in 50 patients with chronic kidney failure]. / Fréquence de l'ischémie myocardique indolore au cours de l'hémodialyse de 50 insuffisants rénaux chroniques.

The authors carried out a prospective study to determine the frequency of silent ischemia (SI) in 50 consecutive patients with end stage renal failure during dialysis by Holter monitoring. Twenty patients had SI (40%). This event was related to the number of cardiovascular risk factors (p = 0.0025), principally diabetes, smoking and the underlying renal disease (p = 0.018), and to a history of coronary artery disease (p = 0.0015). Two patients died during the nine months follow-up period and both had SI on Holter monitoring. Dialysis therapy in anaemic patients may predispose to and facilitate the detection of myocardial ischemia by the simultaneous interplay of hypotension, hypovolemia, hypoxia and tachycardia. The detection of these ischemic events may allow identification of a subgroup of dialysis patients with a high cardiovascular risk. The prognosis of these patients and best therapeutic approach require further study.

Mucosal immunity in adult primary glomerulonephritis. I. Evaluation of salivary IgA subclasses and components.

Salivary components (proteins, albumin, IgA1, IgA2, IgG, IgM, beta 2-microglobulin, neopterin and peroxidase) were investigated in 3 adult types of primary glomerulonephritis (PGN): IgA mesangial glomerulonephritis (IgAGN; n = 14); idiopathic membranous glomerulonephritis (n = 8); idiopathic nephrotic syndrome (INS; n = 14), and a control group (n = 11). Salivary IgA1 levels were significantly increased in all these PGN whereas salivary IgA2 levels were only higher than controls in INS. Albumin and proteins did not differ between PGN and controls, while the IgA1 + IgA2/protein ratio was significantly increased in these 3 PGN. Salivary neopterin levels were enhanced in the 3 types of PGN, whereas beta 2-microglobulin levels were not. The other salivary components did not differ from controls. These results demonstrate the nonspecificity of the IgA increase at mucosal sites previously found in IgAGN and raise the hypothesis of an activation of mucosal immunity of PGN or of a disturbed isotypic network or lymphokine secretion in these diseases.

[Significance of IGA antigliadin antibodies during primary glomerulonephritis with mesangial IGA deposits]. / Signification des anticorps IgA antigliadine au cours des glomérulonéphrites primitives avec dépôts mésangiaux d'IgA.

The association of IgA anti-gliadin antibodies and IgA glomerulonephritis (IgA GN) was first reported in 1987 (Am J Nephrol, 1987, 7, 178-183) and has since been confirmed by other groups. We have developed a second generation ELISA (alkaline phosphatase, biotin-avidin) and used it to test 45 adult IgA GN, 34 idiopathic membranous nephropathy (MN), 31 idiopathic nephrotic syndrome (INS), and 11 idiopathic membranoproliferative glomerulonephritis (MPG) patients. IgA anti-gliadin antibodies were found in 24 IgA GN (53%), 1 MN (3%), 1 INS (3%), and 1 MGP (9%) patients. The presence of these antibodies in a patient with proteinuria strongly suggests IgA GN, with a sensitivity of 53%, a specificity of 96%, a positive predictive value of 88% and a negative predictive value of 77%. The presence of IgA anti-gliadin antibodies in IgA GN did not necessarily indicate coeliac disease because: a) neither IgG nor IgA anti-reticulin nor IgA anti-endomysium antibodies were found; b) intestinal absorption tests (folates, EDTA) were normal; c) biopsies of the small intestine were normal; and d) a gluten-free diet did not alter the evolution of the disease. Immunochemical analysis (footprinting after separation of the gliadins by rocket electrophoresis) showed the variability of the fractions recognized by the IgA antibodies from patients and controls, in addition to the absence of a typical profile. Gliadin does not have a lectin effect, since mannan and mannose did not inhibit the ELISA. Immunofluorescent labeling of human kidney with purified rabbit IgG anti-gliadin antibodies did not reveal a common epitope shared by gliadin and renal structures.(ABSTRACT TRUNCATED AT 250 WORDS)