Monocyte-macrophage system function in primary IgA nephropathy.
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Biomedical subjects
Publications and source records attributed to R Coppo.
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The distribution of IgA subclasses in IgA immune complexes (IgA IC) in sera of patients with primary IgA glomerulonephritis and Henoch-Schönlein purpura nephritis was analysed. High levels of IgA IC containing both IgA1 and IgA2 subclasses were present in correlation with the phases of clinical activity. In these nephropathies the finding of IgA subclass distribution in IgA IC similar to that found in secretions may add further support to the hypothesis that IgA IC are of mucosal origin, albeit a primary derangement of the humoral immune system in these patients cannot be disregarded.
The Fc-receptor function of macrophages and monocytes was studied in 10 healthy subjects and 10 patients (5 in phase of clinical activity) affected by systemic vasculitis with histological evidence of renal involvement. Macrophage function was detected by measuring the clearance in vivo of IgG-sensitized 51Cr-labelled autologous red blood cells (RBC). In vitro immune phagocytosis of monocytes was analysed as a kinetic phenomenon by incubating IgG-coated RBC with nearly pure suspensions of peripheral monocytes. All 5 patients studied in phase of clinical activity showed a defective Fc-receptor function in both the assays, as compared with normal subjects. Since a good correlation was found between the in vitro and the in vivo methods, the use of this non-invasive in vitro procedure is proposed as a substitute for the radioactive in vivo techniques in monitoring the course of the above disease.
22 patients with immune complex (IC) glomerulonephritis (GN) were treated with plasma exchange (PE), corticosteroids and immunosuppressors, in 4 cases also as a long treatment. We evaluated circulating IC and some neutrophils (PMN) functions such as phagocytosis, aggregation and platelet activating factor (PAF) release. In extracapillary GN improvement was observed in 3/9 patients, concomitantly with IC decrease: in 6/9 patients no renal amelioration occurred, despite IC decrease in two. In all Lupus Nephritis and mixed IgG/IgM cryoglobulinemia, IC were highly positive and the disappearance of IC in 5/6 Lupus Nephritis and 4/4 cryoglobulinemia heralded systemic and renal amelioration. PMN functions were hampered in acute Lupus Nephritis and mixed cryoglobulinemia, but constantly improved along with IC decrease and clinical amelioration. Thus in extracapillary GN the decrease of IC by PE may not eventuate in renal improvement. In Lupus Nephritis and cryoglobulinemia a better correlation exits between IC, PMN function and clinical course.
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IgA subclasses in circulating immune complexes (IgA1IC), serum immunoglobulins and mesangial deposits in Berger's and Schönlein-Henoch glomerulonephritis (GN) were studied. Both IgA1IC and IgA2IC were significantly higher in Berger's and Schönlein-Henoch GN than in healthy people. In phases of clinical activity both IgAIC subclasses further increased. The IgA1/IgA2 ratio was found not to differ from controls in either groups of patients. An increase in polymeric IgA was observed in Berger's and in Schönlein-Henoch GN. Both IgA subclasses were found in mesangial deposits.
In nine patients with IgA nephropathy, the function of the mononuclear phagocyte system was assessed by measuring in vivo clearance of anti-D coated red blood cells (RBC) and in vitro phagocytosis of sensitised RBC by monocytes. A strict correlation was found between in vivo macrophage function and in vitro monocyte phagocytosis. Statistical correlations were also found between in vivo clearance values and IgAIC and C3d values. A defective macrophage and monocyte function affects patients with major signs of clinical activity, highest IgAIC values, signs of complement activation and the most unfavourable clinical course.
To evaluate the effect of transfusion on immunity, we studied some immunological parameters in 14 uremic patients treated with 3 blood transfusions (5 with HLA-compatible and 9 with random transfusions). Before transfusions 8/14 patients were DNCB-negative; both spontaneous and active E-rosettes were below normal range. The parameters of humoral immunity (S-Ig, C3, C4, IC, CRP) were normal. After both the first and second transfusions an increase in T- and B-lymphocytes was found. The third transfusion led to a more pronounced and prolonged immunosuppression in patients treated with compatible transfusions than in those treated with random transfusions. Our findings suggest that blood transfusion--HLA-compatible transfusion in particular--results in an impairment of the lymphocyte role.
32 patients (22 biopsed) with lupus nephritis (LN) were observed for circulating immune complexes (IC). Solid phase C1q (SPC1q) and polyethylene glycol (PEG) precipitation tests were used. The patients were studied during the clinical follow-up in different phases of disease activity. Comparative studies between each histological class of LN and corresponding forms of idiopathic glomerulonephritis (IGN) were made: no significant differences were found between either mesangial LN and stalk mesangial IGN, or between focal proliferative LN an focal proliferative IGN. However, a significant difference was found for SPC1q data between diffuse proliferative LN and mesangiocapillary IGN, and between membranous LN and membranous IGN. LN, with an acute nephritic syndrome and hypocomplementemia, displayed SPC1q data significantly above the levels of IC found in IGN with similar clinical features. IC serum data would seem an important element for the diagnosis and the clinical management of patients affected by LN.
A new conglutinin solid phase assay for the detection of immune complexes containing IgA (IgAIC) and other conglutinin tests for immune complexes containing IgG and IgM (IgGIC and IgMIC) were used in studies on 34 patients affected by Berger's GN (92 sera) and 12 affected by Henoch-Schoenlein GN (61 sera). Thirty-six patients were observed over follow-up periods of 2-43 months. Levels of IgAIC in both groups of patients were significantly higher than those in healthy people. The values obtained in patients with Henoch-Schoenlein GN were statistically higher than those obtained in patients with Berger's GN. Moreover, IgAIC were frequently found to be associated with IgGIC and/or IgMIC. In both groups of patients, the IgAIC levels were significantly correlated with the presence of signs of clinical and histological activity such as the magnitude of microscopic hematuria, a past history of macroscopic hematuria and the percentage of glomeruli with florid epithelial crescents.
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In spite of the anticoagulant activity of heparin platelet deposition and contact activation of coagulation occurs during dialysis. We have studied platelet counts, fibrinogen, platelet factor 4, beta-thromboglobulin, thromboxane B2, FRA, C3d and kallikrein values, whole blood and euglobulin lysis times and membrane areas in haemodialysis using cuprophan and cellulose acetate and in haemofiltration with polyacrilonitrile. Deposits on all the three membranes included leucocytes, platelets and fibrin. The coagulation and fibrinolytic systems are activated more intensively with cellulose acetate and more prolongedly with polyacrilonitrile. Platelet factor 4 and beta-thromboglobulin increases suggest platelet activation, only partially dependent on arachidonic acid-mediated pathway as thromboxane B2 is not increased. The complement system is activated whereas serum kallikrein does not alter, suggesting that platelets rather than factor XII are crucial in contact activation.
To evaluate the effect of transfusion on immunity, 14 uraemic patients treated with 3 blood transfusions from a single donor, at weekly intervals, were studied: in 5 cases HLA-A,B were compatible, in 9 cases they were not. As markers of cellular and humoral immunity DNCB, PPD skin tests, spontaneous and active E-rosettes, EAC-rosettes, surface membrane immunoglobulins, C3, C4, C3d, serum immunoglobulins, circulating immune complexes and C-reactive protein were investigated. This protocol was applied before transfusions, 1 week after each transfusion (day +7, +14, +21) and 20 weeks later (day +80). Before transfusions 8/14 patients were DNCB negative; both spontaneous and active E-rosettes were below normal range. The other parameters were normal. On day +7 T and B lymphocytes were increased, while the other parameters were unmodified. On day +21 there was a significant reduction (p less than 0.5) in T lymphocytes in patients treated with compatible transfusions. On day +80 3/3 DNCB positive patients, treated with compatible transfusions, became negative and 1/3 DNCB positive patients, treated with random transfusions, also became negative. Three/fourteen patients showed a decrease in B lymphocytes. The other results were unchanged. Our preliminary results suggest that transfusions, either from an HLA compatible donor or not, can impair lymphocyte function.
Eleven cases of glomerulonephritis with dense deposits were selected on the basis of electron microscopic examination performed either on material treated according to conventional techniques (9 cases) or on previously paraffin-embedded material (2 cases). While uniform immunohistochemical patterns were observed, different features were shown by light microscopy: in only 3 cases were membranoproliferative or lobular patterns present, while in the others a varying degree of mesangial cell proliferation (moderate, mild or even very scanty with focal and segmental distribution) was detected. The generally accepted statement that glomerulonephritis with dense deposits represents a subgroup of membranoproliferative glomerulonephritis therefore seems questionable. In addition to several clinical and serological data, these morphological features give further support to the hypothesis that glomerulonephritis with dense deposits in all respects a peculiar and distinct form of glomerulonephritis.
Twenty-nine patients with Systemic Lupus Erythematosus (SLE) and 6 patients with Acute Poststreptococcal Glomerulonephritis (APGN) have been studied with the polymorphonuclear neutrophil (PMN) immunohistological technique to detect in vivo interaction between circulating immune complexes (IC) and PMN membrane receptors. Patients have been studied both at diagnosis and during follow-up and the results compared to those yielded by the C1qSP test. Our data provide evidence that the PMN immunohistological technique may prove a useful tool in monitoring IC disease. Moreover, elution studies may allow the detection and characterization of the antigens in the PMN-bound IC.
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