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Bence Jones proteinuria (BJP) refers to monoclonal free immunoglobulin light chains detected in urine, deriving from the clonal expansion of plasma cells in the bone marrow in patients with plasma cell dyscrasias, associated with monoclonal gammopathies of uncertain origin. This review summarizes routinely diagnostic procedures to assess BJP highlighting critical steps of pre-analytical, analytical, and post-analytical phases.The best option for BJP detection is the first morning void urine sample and immunofixation electrophoresis detection technique (IFE) the recommended method, with the employment of specific polyvalent antisera. Other qualitative tests for a quick evaluation of BJP are currently available. Densitometric analysis performed on the 24-hour urine is the recommended method to quantify BJP. To overcome the 24-hour collection, it is possible to use morning urine sample and correlate the assessed value of BJP to creatininuria. In addition to the traditional ones, we here reviewed screening methods currently used to avoid false negatives and reduce the time around test (TAT), together with immunochemical quantification methods for increased sensitivity, after checking BJP by IFE. Mass spectrometry emerges as a new challenge in the determination of BJP.The employment of different based-assays methods may be useful for diagnostic purposes to improve the accuracy of BJP monitoring in monoclonal gammopathies.

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and hyperinsulinemia that contribute to create a state of chronic low-grade inflammation. We performed an observational case-control study to investigate inflammatory and immunological parameters, such as IgG subclasses and free light chains (FLCs) and hemolytic complement activity (CH50) in non-obese PCOS, evaluating their relations with metabolic and hormonal parameters.36 subjects were studied: 16 PCOS patients (mean±SEM 27.13±1.82 age; BMI 24.1±0.9 kg/m2); 20 controls (aged 26.05±0.73; BMI 20.8 ± 0.4 kg/m2). The blood sample was collected for metabolic and hormonal parameters, IgG subclasses, k and λ FLCs, CH50. Hormones were measured by immunochemiluminometric assays; metabolic parameters by enzymatic assays; subclasses of IgG, FLCs, and CH50 were evaluated by the turbidimetric method.PCOS patients showed vs. controls lower IgG1, IgG2, IgG3 (mean±SEM 3.76±0.29 g/l, 2.63±0.20, 0.62±0.06, 0.34±0.08 vs. 6.49±0.35, 4.28±0.25, 0.84±0.07, 0.33±0.04, respectively) and higher levels of FLCs (k 12.22±0.71 vs. 6.03±0.30, λ 10.10±0.79 vs. 8.04±0.48 g/l) and CH50 (48.64±2.65 vs. 36.51±1.38 U/ml); we found correlation between IgG2 and free-testosterone (r=0.72, p=0.005) and CH50 and vitamin D (r=0.54, p=0.04); an inverse correlation was found between IgG1 and, respectively, ACTH (r=-0.57, p=0.02) and cortisol (r=0.78, p=0.001) in PCOS.In the complex scenario of low-grade inflammation in non-obese PCOS, we showed lower levels of main subclasses of IgG and higher CH50 levels, suggesting the involvement of other mechanisms other than the "classical" pathway of complement activation; FLCs could be attractive to monitor inflammation degree, disease activity and influence on hormonal status.

A still uncertain association between vitamin D levels and HCV chronic liver diseases has been reported. Increased levels of serum-free light chains (FLCs) and an altered k/λ FLC ratio correlate with Mixed Cryoglobulinemia (MC) vasculitis and/or B-cell non-Hodgkin's lymphoma in HCV-positive patients. We aimed to investigate the possible role of vitamin D, vitamin D Binding Protein (DBP), and FLCs levels as a tool for discriminating different stages of HCV- related MC and chronic liver diseases.Sixty-five untreated patients were retrospectively enrolled and 21 healthy blood donors (HBD) were used as controls. Vitamin D, DBP, FLCs, and cryoglobulins levels were measured. Based on cryoglobulins, patients were divided in three subgroups (without cryoglobulins, type II, and type III).We didn't find any significant differences in vitamin D and DBP levels between HCV patients' main groups and HBD. Serum FLCs levels were significantly higher in HCV patients than in HBD. FLCs ratio among patients' subgroups did not reveal differences.Our results confirm the presence of an increased serum level of FLCs in HCV patients and suggest that nor vitamin D and DBP or FLC levels can be considered reliable biomarkers for discriminating different stages of HCV-associated chronic liver diseases and/or HCV-associated extrahepatic manifestation. We confirm that serological FLCs levels are significantly higher in patients than in HBD as a signature of B cell activation in course of HCV infection.

Monoclonal plasma cell proliferative disorders comprise a wide spectrum of diseases associated to clonal B-cell expansion. Serum protein electrophoretic profile (SPEP) and circulating free light chains (FLCs) levels are the mainstay of diseases management. Recently, soluble (s) Syndecan-1 (SDC1, CD138) produced by myeloma plasma cells has been suggested in the monitoring and follow-up of patients with myeloma. The aim of our study is to evaluate sCD138 in addition with FLCs and SPEP for the screening of patients with different evolutive disease pathways.Sera from 73 patients with monoclonal gammopathy of undetermined significance (MGUS), 120 smoldering and 42 multiple myeloma (SMM and MM, respectively), 70 HCV-related mixed cryoglobulinemia (MC), 35 B-cell non-Hodgkin's lymphoma (B-NHL) and sera from 50 healthy donors (HD), were tested for sCD138, FLCs (assessed by means of ELISA and turbidimetric assay, respectively) and electrophoresis pattern (performed on Capillarys system) for the generation of a novel biomarker score (BS).Our results were grouped according to the two main lines of disease progression (vs. MM or B-NHL): in one group we found BS mean values of 0.2, 3.4, 5.3, 7.1 for HD, MGUS, SMM and MM, respectively; in the other group of 0.2, 4.4, 6.7 for HD, MC and B-NHL.We showed that BS mean values follow the ingravescence disease status towards the two main lines of progression to cancerous conditions; it could represent an additional useful tool in the management of screening and/or follow-up.

Pheochromocytoma is a catecholamine-producing tumor of the sympathetic nervous system which in 4-14% of the cases may be malignant. The differentiation between benign and malignant phoechromocytomas is very difficult, the presence of metastatic lesions and gross invasion into surrounding tissues are the lonely accettable parameters to confirm malignancy. Since the patients with malignant pheochromocytomas have a very poor survival rate, care must be taken for an early detections and a careful follow up. Three cases of malignant pheochromocytoma are reported. In one of these cases the tumor was a functioning mass; the other two cases presented by a hemorrhagic complication. A careful review of the pertinent literature allows to outline the correct approach to this rare pathology as for the diagnosis and the treatment, also including the actual criteria to establish its malignancy.

Summary Where practicable, all subjects found with onset-phase-four blood pressure of 90 mmHg or more after referral were allocated, on a random basis, to alternative antihypertensive regimes at a dosage related to response. Of those 110 receiving either guanethidine, methyldopa or debrisoquine, only the group on methyldopa had significantly reduced median blood pressure by two out of four criteria and after 6 months of therapy. It is nevertheless considered that by assessment of the total group more significant conclusions can be drawn for an eventual attempt to control hypertension on a community basis than by studies of highly selected groups treated under unusually favourable conditions.