Search

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.

Patients with total hip arthroplasty were screened for the presence of proinflammatory cytokines in the systemic circulation. Only increased levels of interleukin-6 were detected in patients having had total hip arthroplasty more than 10 years ago. These increased levels of interleukin-6 were associated with a decrease in bone mineral density associated with polyethylene wear and with radiologic osteolysis in some patients. These abnormalities were not found in control subjects without total hip arthroplasty or in patients who had a prosthesis in place for less than 6 years. The elevation in interleukin-6 levels found in patients with the oldest prostheses could constitute a marker for periprosthetic osteolysis.

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.

Serum IgG subclass levels were measured using a competitive indirect immunoenzymatic assay with monoclonal antibodies in 22 acute myeloid leukemia patients at presentation and prior to specific therapy. Three patients had moderate IgG1 deficiency and 1 moderate IgG3 deficiency. Two of the three IgG1 deficient patients (and only one other) failed to respond to induction chemotherapy and the third died of bone marrow aplasia during induction.

The polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes (POEMS) syndrome is a rare multisystem disorder of obscure pathogenesis associated with osteosclerotic myeloma. Circulating levels of proinflammatory cytokines (tumor necrosis factor-alpha (TNF-alpha) interleukin-1 beta [IL-1 beta], IL-2, IL-6, and interferon-gamma [IFN-gamma]), anti-inflammatory cytokines (transforming growth factor beta 1 [TGF beta 1], IL-4, IL-10, and IL-13), the cytokine carrier protein alpha 2 macroglobulin, IL-1 receptor antagonist (IL-1ra), soluble TNF receptors (sTNFr) p55 and p75, and soluble IL-6 receptor (sIL-6r) were determined in 15 patients with POEMS syndrome and 15 with multiple myeloma. Patients with POEMS syndrome had higher serum levels of IL-1 beta, TNF-alpha, and IL-6 and lower serum levels of TGF beta 1 than did patients with multiple myeloma. Serum levels of IL-2, IL-4, IL-10, IL-13, IFN-gamma, alpha 2 macroglobulin, and sIL-6r were similar in both groups. IL-1ra and sTNFrs were increased in POEMS syndrome, but out of proportion to the increase of IL-1 beta and TNF-alpha. Serial evaluations in 1 patient showed that proinflammatory cytokine serum levels paralleled disease activity assessed by platelet count and neurologic involvement. Our results suggest that the manifestations of POEMS syndrome might be regarded as the result of a marked activation of the proinflammatory cytokine network (IL-1 beta, IL-6, and TNF-alpha) associated with a weak or even decreased (TGF beta 1) antagonistic reaction insufficient to counteract the noxious effects of cytokines.