Similarities and differences between pediatric and adult patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease with highest prevalence among women of childbearing age. However, children younger than 16 years also can develop SLE (childhood-onset lupus/juvenile-type SLE). The aim of our study was to compare the clinical course of adult and pediatric-onset SLE. Data from 342 adult patients followed at the University of Debrecen, Hungary, and 79 children documented in the Hungarian National Pediatric SLE registry were analyzed using hospital medical records. Organ manifestations, laboratory parameters, and immunoserological characteristics were reviewed and the results were evaluated using SPSS for Windows software.Gender distribution was not significantly different between groups with disease starting in childhood vs adulthood. The prevalence of the following manifestations was significantly higher for pediatric than for adult-onset disease including: lupus nephritis (43% pediatric vs 26.4% for adult-onset), hematological disorders (57% vs 36.4%), photosensitivity (20% vs 9%), butterfly rash (61% vs 35.5%) and mucosal ulceration (11.4% vs 4%). For adult-onset SLE, neurological symptoms (30% vs 6%) and polyarthritis (86% vs 68%) occurred significantly more frequently than in children. Anti-SSA, anti-SSB and antiphospholipid antibodies were detected at significantly higher levels in adult-onset patients compared to those in pediatrics. Children were more commonly given high-dose intravenous immunoglobulin treatment (6.3% vs 0.6%) and mycophenolate mofetil (15.2% vs 5.3%) than adults.These results suggest that pediatric and adult-onset SLE differ in multiple aspects, and it is important to recognize these differences for optimal treatment and prognosis of these patients.

Decreased apopto-phagocytic gene expression in the macrophages of systemic lupus erythematosus patients.

The clearance of apoptotic cells has an important role in the maintenance of tissue homeostasis and in the protection of tissues from the inflammatory and immunogenic contents of dying cells. A defect in the recognition and phagocytosis of apoptotic cells contributes to the development of chronic inflammation and autoimmune disorders. We have observed that compared with healthy donors, differentiated macrophages from patients with untreated systemic lupus erythematosus (SLE) showed decreased phagocytosis of apoptotic neutrophils. A TaqMan Low Density Array was designed to determine the mRNA expression levels of 95 apopto-phagocytic genes in differentiated non-phagocytosing and phagocytosing macrophages. In the macrophages of clinically and immunoserologically active SLE patients, 39 genes were expressed at lower levels than in the control macrophages. When inactive patients were compared with those with minor immunoserological abnormalities or patients in an immunoserologically active state, a relationship was observed between the altered gene expression profile and the disease state. In the macrophages of patients with engulfing apoptotic cells, an upregulation of genes involved in inflammation, autophagy, and signaling was observed. These results indicate that novel immune-pathological pathways are involved in SLE and suggest targets for potential therapeutic modulation.

Distinct phenotypes in mixed connective tissue disease: subgroups and survival.

The aim of the present study was to assess the autoantibody profile, dominant clinical symptoms and cluster characteristics of different mixed connective tissue disease (MCTD phenotypes. Two-hundred-and-one patients with MCTD were followed-up longitudinally. Five clinical parameters, Raynaud's phenomenon, pulmonary artery hypertension (PAH), myositis, interstitial lung disease (ILD), erosive arthritis and five auto-antibodies besides anti-U1RNP, antiendothelial cell antibodies (AECA), anti-CCP, anti-cardiolipin (anti-CL), anti-SSA/SSB and IgM rheumatoid factor (RF) were selected for cluster analysis. The mean age of patients was 52.9 ± 12.4 years and the mean follow-up of the disease was 12.5 ± 7.2 years. Patients were classified into three cluster groups. Cluster 1 with 77 patients, cluster 2 with 79 patients and cluster 3 with 45 patients. In cluster 1 the prevalence of PAH (55.8%; p < 0.001), Raynaud's phenomenon (92.2%; p < 0.001) and livedo reticularis (24.6%, p < 0.001) was significantly greater than in cluster 2 and 3. In cluster 2, the incidence of ILD (98.7%; p < 0.001), myositis (77.2%; p < 0.001), and esophageal dysmotility (89.8%; p < 0.001) was significantly greater than that in cluster 1 and 3. In cluster 3, anti-CCP antibodies were present in 31 of 45 patients (68.8%) with erosions. Anti-CCP antibodies were present in 37 of 42 patients (88.0%) with erosions. PAH, angina, venous thrombosis was observed in cluster 1 and pulmonary fibrosis in cluster 2, musculosceletal damage, gastrointestinal symptoms and osteoporotic fractures were most frequent in cluster 3. Cumulative survival assessment indicated cluster 1 patients having the worst prognosis. Cluster analysis is valuable to differentiate among various subsets of MCTD and useful prognostic factor regarding the disease course.

Immunological reconstitution after autologous stem cell transplantation in patients with refractory systemic autoimmune diseases.

OBJECTIVE: High-dose chemotherapy followed by autologous haematopoietic stem cell transplantation (AHSCT) can be a salvage therapy for patients with severe, refractory systemic autoimmune diseases. The function of the newly rebuilt immune system is important, but little is known about immune reconstitution after AHSCT in autoimmune disorders. Our aim was to investigate the repopulation of different lymphocyte subsets in patients with systemic autoimmune diseases after AHSCT. METHODS: Twelve patients with severe refractory, autoimmune diseases were enrolled in the study: four with rheumatoid arthritis (RA), four with systemic sclerosis (SSc), three with systemic lupus erythematosus (SLE), and one with autoimmune overlap syndrome (myositis and RA). After stem-cell mobilization, CD34+ apheresis was carried out, followed by conditioning and AHSCT. After transplantation, peripheral lymphocyte subsets were regularly assessed by flow cytometry. RESULTS: The follow-up time was 24 months. The overall transplantation-related mortality (TRM) was 16.7% and the transplant-related toxicity was 33% 2 years after AHSCT. Regarding the immune reconstitution, CD56+ natural killer (NK) cells appeared in the earliest phase after transplantation, followed by CD8+ T cells. B cells and CD4+ T cells became normal within 150 days. The ratio of naive cells was low 30 days after AHSCT; however, naive B cells regenerated within 2 months whereas the repopulation of naive T cells took longer. After a short increase, the ratio of memory cells decreased 2 months after transplantation. Regulatory T (Treg) cells did not change significantly in the peritransplant period. Altogether approximately 5-6 months were required for the reconstitution of the peripheral immune network. CONCLUSIONS: AHSCT can be a salvage therapeutic modality in autoimmune patients who are refractory to other conventional therapies.

Serum and urinary cytokine levels of SLE patients.

Systemic lupus erythematosus (SLE) is a chronic, relapsing, polysystemic autoimmune disease with various clinical signs. The prognosis of SLE patients is influenced by neuropsychiatric and renal involvement. Lupus nephritis (LN) is present in 40-60% of patients. Classical laboratory parameters are not sensitive and specific in prediction renal flares, over the last few years there has been a growing interest in searching novel lupus biomarkers predicting future flares. Our goal was to detect serum and urinary level of cytokines in 36 patients with lupus nephritis (34 female and 2 male, mean age: 43.36 +/- 11.53 years), 23 patients with SLE without renal involvement (19 women and 4 men, mean age: 54 +/- 8.71) (both groups followed by the 3rd Department of Internal Medicine, Division of Clinical Immunology, University of Debrecen) and 30 healthy controls (23 female and 7 male, mean age: 45.5 +/- 12.4). Serum IL-1 (interleukin), IL-2 (both p < 0.05), IL-6, IL-13 and IFN-gamma (p < 0.001) levels were significantly higher in lupus nephritis patients, as compared to patients with SLE without renal involvement and healthy controls. Urinary level of IL-1 and TNF-alpha were significantly higher in SLE patients without renal disease (p = 0.012 and p < 0.001), while urinary IFN-gamma was significantly higher in LN patients (p = 0.002). Measurement of IL-6 level in SLE patients could help to predict future renal involvement of SLE patients.

The immunopathological role of vitamin D in patients with SLE: data from a single centre registry in Hungary.

OBJECTIVES: Disproportionate vitamin D levels may play an important role in the development of certain systemic autoimmune and rheumatic diseases. The aim of the present study was to investigate the prevalence of vitamin D insufficiency in patients with systemic lupus erythematosus (SLE) and to compare serological and clinical parameters in patients with different vitamin D levels from a single centre registry in Central-Eastern Europe. METHODS: A total of 177 patients with SLE were enrolled in the study. 25-Hydroxyvitamin D [25(OH)D] levels were measured by chemiluminescent immunoassay (CLIA). Autoantibody profiles, complement 3 (C3) and C4, clinical symptoms, and disease activity (using the SLE disease activity index, SLEDAI) of the patients were assessed. RESULTS: Vitamin D concentration in the total SLE group investigated was 26.88 ± 13.25 ng/mL. Vitamin D levels were normal (≥ 30 ng/mL) in 18.1% of patients, insufficient (15-30 ng/mL) in 44.6%, and deficient (< 15 ng/mL) in 37.3%. The vitamin levels were significantly reduced in postmenopausal compared to premenopausal patients (p = 0.02). Patients with pericarditis (p = 0.013), neuropsychiatric diseases (p = 0.01), and deep vein thrombosis (p = 0.014) had reduced vitamin D levels. SLEDAI score was significantly increased in patients with reduced vitamin D levels (p = 0.038). Anti-double-stranded (ds)DNA autoantibody concentrations increased from normal to insufficient and further increased from insufficient to deficient patient subsets (p = 0.021). Anti-Smith antigen (anti-Sm) concentrations increased (p < 0.001), C4 levels decreased (p = 0.027), and immunoglobulin (Ig)G concentration increased (p = 0.034) in patients with reduced vitamin D levels. CONCLUSIONS: Our data suggest that vitamin D deficiency in SLE may play a role in perpetuation of the disease.

Clinical and immunoserological characteristics of the transition from primary to overlap antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is a distinct clinical entity characterized by arterial and venous thromboembolic events, recurrent fetal loss and the presence of antiphospholipid antibodies in the patients' sera. In primary APS, there is no detectable underlying disease, while overlap APS is associated with clinical syndromes including systemic autoimmune diseases, infections, or malignancies. We carried out a retrospective analysis of serological and clinical manifestations as well as assessed outcome-measures in 165 patients with primary APS. Thrombotic manifestations and possible signs of autoimmune diseases were determined at the time of the diagnosis, followed by the analysis of recurrent thrombotic events and effects of therapy during the follow-up period. Among the 165 patients with primary APS at onset, 105 patients (63%) remained primary APS after a mean 5.2 years of follow-up. In 14% of the patients, subsequently APS became associated with various characteristics of undifferentiated connective tissue disease. Finally 23% of patients evolved into a definitive systemic autoimmune disease during a mean 9.75 years of follow-up. Recurrent thrombotic events were registered in 24% of patients. Our results suggest that primary APS may be considered as a potential early phase of a dynamic transition towards a well-defined systemic autoimmune disease.

Autologous stem cell transplantation in autoimmune and rheumatic diseases: from the molecular background to clinical applications.

Autoimmune diseases have a multifactorial origin. Because of disturbances of the immune system, autoreactive T and B cells target self-antigens, leading to permanent organ damage. Despite novel therapeutic protocols, the disease course is chronic and in many instances the outcome is lethal. The efficacy of stem cell therapy has been observed in autoimmune animal models and in autoimmune diseases related to haematological abnormalities. Although the therapy is more than 30 years old, its broad spread has been delayed by the serious side-effects due to the conditioning treatments based on oncological protocols. Evaluation of the data of patients who have undergone autologous stem cell therapy reinforced the view that protocols used for conditioning treatments, mostly causing lymphoablation, and procedures carried out in specialist centres significantly reduced mortality, with an almost optimal therapeutical efficacy. New, multicentre investigations have been launched to compare the efficacy of various protocols. In this review, we summarize certain aspects of the molecular background of autologous stem cell transplantation and also depict the response to therapy in various autoimmune and rheumatic diseases.

Impaired regulatory T-cell homeostasis due to vitamin D deficiency in undifferentiated connective tissue disease.

OBJECTIVE: The aim of this study was to perform a quantitative and functional analysis of natural CD4+CD25(high)Foxp3+ regulatory T cells (nTregs) and CD4+IL-17+ T cells, and to assess the serum levels of proinflammatory cytokines in patients with undifferentiated connective tissue disease (UCTD) before and after 5 weeks of 0.5 µg/day alfacalcidol supplementation. METHODS: Twenty-five patients with UCTD were enrolled in an open-label trial of alfacalcidol. Plasma levels of 25-hydroxyvitamin D [25(OH)D] were assessed by a high-performance liquid chromatography (HPLC) method. Flow cytometry was used for the quantification of nTregs and the IL-17 expression of T-helper (Th)17 cells. The serum concentrations of cytokines interleukin (IL)-12, interferon (IFN)-γ, IL-23, IL-17, IL-6, and IL-10 were measured by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Treatment with alfacalcidol raised 25(OH)D levels from a mean of 23.5 ± 5.6 to 34.5 ± 7.4 ng/mL (p = 0.059; NS). Alfacalcidol treatment decreased both Th1- (IL-12 and IFN-γ) and Th17-related (IL-23, IL-17, IL-6) cytokine levels in UCTD patients, while the soluble IL-10 level increased (IL-12: 156.7 ± 75.2 vs. 87.5 ± 42.1 pg/mL, p < 0.001; IFN-γ: 41.5 ± 12.0 vs. 21.7 ± 9.9 pg/mL, p < 0.001; IL-23: 385.2 ± 82.2 vs. 210.0 ± 69.3 pg/mL, p < 0.001; IL-17: 37.8 ± 9.6 vs. 17.8 ± 4.5 pg/mL, p = 0.009; IL-6: 39.4 ± 11.3 vs. 23.5 ± 6.3 pg/mL, p < 0.001, IL-10: 8.4 ± 3.0 vs. 21.4 ± 9.7 pg/mL, p < 0.001). Alfacalcidol improved the Th17/nTreg imbalance, as it inhibited the IL-17 expression of Th17 cells, and increased the number of nTregs. The alfacalcidol might increase the capacity of nTreg cells to suppress the proliferation of autologous CD4+CD25⁻ cells. CONCLUSION: Our findings support the idea that vitamin D influences the Th17/nTreg imbalance in vitamin D-insufficient patients with UCTD and could be beneficial in the management of the disease.

Immunological features of primary anti-phospholipid syndrome in connection with endothelial dysfunction.

OBJECTIVES: To describe how certain peripheral immune parameters reflect the inflammatory alterations in patients with primary APS. METHODS: Twenty-eight patients with newly diagnosed primary APS were studied. The control group included 26 patients with stable coronary disease and 38 healthy individuals. Peripheral blood lymphocyte subgroups were quantified, intracellular cytokines were measured by flow cytometry, soluble cytokines and auto-antibodies were assessed using ELISA. Endothelial dysfunction was evaluated by measuring endothelium-dependent (flow-mediated; FMD) vasodilation. Carotid duplex ultrasound was performed to quantify the carotid artery intima-media thickness (IMT). Stiffness parameters, augmentation index (AIx) and pulse wave velocity (PWV) were assessed by TensioClinic technology. RESULTS: Serum IL-4 and IL-6 levels were significantly higher in APS. CD4+IL10+ and CD8+IL10+ cell percentages in APS were significantly increased compared with controls. Th 0 and T cytotoxic 0 cell percentages were significantly decreased in patients compared with controls. FMD in APS was significantly lower, while IMT was higher than that of controls. FMD showed strong association with stiffness parameters, AIx and PWV. A significant negative linear correlation was detected between PWV and CD8+IL10+ cell percentages and significant positive linear correlation was found between PWV and CD8+IL10- cell percentage. CONCLUSION: In APS, the orchestrated pro-inflammatory cascade can eventually result in endothelial dysfunction, leading to the characteristic vascular abnormalities of the disease.

The complex role of vitamin D in autoimmune diseases.

Vitamin D, besides having well-known control functions of calcium and phosphorus metabolism, bone formation and mineralization, also has a role in the maintenance of immune-homeostasis. The immune-regulatory role of vitamin D affects both the innate and adaptive immune system contributing to the immune-tolerance of self-structures. Impaired vitamin D supply/regulation, amongst other factors, leads to the development of autoimmune processes in animal models of various autoimmune diseases. The administration of vitamin D in these animals leads to improvement of immune-mediated symptoms. Moreover, in human autoimmune diseases, such as multiple sclerosis, or rheumatoid arthritis the pathogenic role of vitamin D has been described. The review aims at describing the complex immune-regulatory role of vitamin D from the cellular level through autoimmune animal models and depicting the known contribution of vitamin D in the pathogenesis of human autoimmune diseases.

Anti-cyclic citrullinated peptide antibody isotypes in rheumatoid arthritis: association with disease duration, rheumatoid factor production and the presence of shared epitope.

OBJECTIVE: Anti-cyclic citrullinated peptide (anti-CCP) antibodies of IgG isotype are specific diagnostic markers of rheumatoid arthritis (RA). Recent evidence also points to their direct involvement in the pathophysiology. Little information is available, however, regarding the isotype distribution of anti-CCP antibodies and the characteristics of IgA and IgM anti-CCP. METHODS: IgG, IgA and IgM anti-CCP2 and rheumatoid factor (RF) levels were measured in the sera of 119 RA patients and 118 controls, including patients with other rheumatic diseases and healthy subjects. We analyzed the diagnostic performance of IgA and IgM anti-CCP2 antibodies and their relationship with IgG anti-CCP2, RFs, disease duration and the presence of HLA-DRB1 shared epitope (SE) alleles. RESULTS: Patients with RA had significantly higher serum IgA and IgM anti-CCP2 antibody levels than healthy subjects and patients with other rheumatic diseases (p<0.0001). IgG, IgA and IgM anti-CCP2 antibodies were present in 74.8%, 52.9% and 44.5% of RA patients, and their diagnostic specificity was 95.8%, 95.8% and 91.6%, respectively. The presence of anti-CCP2 antibodies was significantly associated with SE alleles (p=0.03). The frequency of IgM anti-CCP2 positivity was lower in longstanding disease compared to early RA (p=0.03). CONCLUSION: IgA and IgM anti-CCP2 antibodies are present in RA patients, and they are similarly specific for RA as IgG anti-CCP2. The higher frequency of IgM anti-CCP2 antibodies in early RA suggests that they are mostly generated during the first phase of immune response; nonetheless, their production seems to be sustained in some patients. Further analysis of IgM and IgA anti-CCP2 antibodies may provide insights into the pathogenesis of RA.

Diagnostic significance of HLA-DQ typing in patients with previous coeliac disease diagnosis based on histology alone.

BACKGROUND: Coeliac disease is strongly associated with human leukocyte antigen (HLA)-DQ2 or DQ8 genotypes. The diagnosis is based on demonstrating crypt-hyperplastic villous atrophy, endomysial or transglutaminase antibodies and correlation of disease activity with gluten intake. AIM: To evaluate the clinical utility of HLA-DQ typing, when coeliac disease diagnosis had previously been established solely by histology. METHODS: HLA-DQ alleles, endomysial and transglutaminase antibodies were investigated and histology slides reviewed in 70 patients diagnosed 2-25 years earlier by small-intestinal biopsy but without measuring endomysial or transglutaminase antibodies. Patients without DQ2 or DQ8 or without unequivocal villous atrophy were followed-up on free diet by using serology and biopsies. RESULTS: All 40 endomysial/transglutaminase antibodies positive patients carried DQ2 or DQ8, and 39 of them had severe villous atrophy. Only 56% of patients without endomysial or transglutaminase antibodies positivity had DQ2 or DQ8 (P < 0.001). Seropositivity and relapse developed in 4 of 11 DQ2 positive but in none of 15 DQ2 and DQ8 negative patients on long-term gluten exposure. CONCLUSIONS: Coeliac disease diagnosis based solely on histology is not always reliable. HLA-DQ typing is important in identifying DQ2 and DQ8 negative subjects who need revision of their diagnosis, but it does not have additive diagnostic value if endomysial positivity is already known.

Increased cytotoxic sensitivity of YPC-1 tumor cells from mice treated with nitrosoureas.

The relative cytotoxic sensitivity of the YPC-1 tumor target cells from untreated mice and from animals treated with nitrosoureas was determined. The amount of 51Cr released from target cells increased significantly when the cells were obtained from treated mice. On the basis of the results of cold-target cytotoxicity inhibition assay, this enhancement was shown to be haplotype specific. The amount of 51Cr released from target cells of mice treated with N,N'-bis(chloroethyl)-N-nitrosourea decreased significantly when the tumor cells were first incubated with fibrinogen and transglutaminase. Based on these results and other published data, a model system is suggested. The model is based on the observation that tumors, and thus tumor antigens, at the cell surface are partly or completely covered by fibrinogen or fibrin. The enzyme transglutaminase is involved in the binding of the fibrinogen or fibrin to the cell surface. Accordingly, it is hypothesized that the nitrosoureas have a dual mode of immunotherapeutic activity. The carbamoylating properties inhibit the fibrin-binding activity of transglutaminase, thus preventing fibrin from covering up or coating the tumor cells and preventing the ability of sensitized effector cells to recognize the tumor-specific antigens in association with self H-2 antigens. The alkylating property of the nitrosoureas mainly concerns reactivity with the DNA of the tumor cells.

Different effects of an oligonucleotide uptake stimulating protein on leukemic cells in their primitive and differentiated state.

The single stranded [3H]oligonucleotide uptake by HL-60 human promyelocyte and K562 human erythroleukemia cells was stimulated 20-45-fold by DUSF (DNA uptake stimulating protein), and this effect was drastically reduced (to 1.6-13x) if the cells were induced to differentiate. The oligonucleotide uptake stimulating effect of DUSF was not altered in HL-60 and K562 cells, if the proliferation of the cells was inhibited by hydroxyurea (HU) treatment. The oligonucleotide uptake by separated granulocytes and mononuclear cells from healthy donors was not stimulated by DUSF, while the uptake of oligonucleotides by myeloid and lymphoid leukemic cells was greatly stimulated (10-15x). The uptake of oligonucleotides by differentiated mononuclear cells of healthy donors could not be stimulated by DUSF, but the oligonucleotide uptake was greatly increased (11x) by DUSF if the cells were subjected to blast transformation.

Enzyme-linked immunosorbent assay for antibodies to native DNA in sera of patients with SLE.

A micro-ELISA technique has been developed to measure antibodies to native DNA and used in SLE patients. The distribution of antibody to native DNA in the main immunoglobulin classes was studied, using anti-human globulin conjugates labelled with peroxidase. the antigen (double-stranded DNA from calf thymus) used in the assay was adsorbed to the surface of polystyrene plates treated with methylated bovine serum albumin. The standardization of the method was carried out by use of globulin calibration curves.

Evaluation of different methods for detecting circulating immune complexes. An inter-laboratory study.

Forty serum samples of healthy blood donors and 60 sera of SLE patients were tested in parallel by 7 different assays for detecting immune complexes. Significantly higher titres and significant higher incidence of positive results were observed in the patient group than in the control group in 6 tests. No test discriminated between patients in an active stage of the disease and those whose disease was inactive. Significantly higher immune complex levels were found in lupus nephritis than in the non-nephritic patients by the complement consumption test. Significant positive correlation was obtained between the results of the macrophage aggregated IgG uptake inhibition and PEG-precipitation tests and between two tests based on the interaction of the complexes with the complement system. A characteristic 'profile' of the immune complex assay was observed in the course of the repeated testings of the same patients. The results indicate that the different methods detect different types of immune complexes present in the blood of the patients.

Evaluation of different methods for detecting circulating immune complexes. Studies in patients with lung cancer.

In a collaborative study involving 7 laboratories, sera from 53 patients with lung cancer, 37 primary and 16 secondary tumours, and sera of 40 healthy blood donors were tested by 19 different assays or assay modifications used for detecting immune complexes. In 12 out of 19 assays, significantly higher immune complex levels were found in the cancer patients than in the healthy subjects. Assays based on interactions between immune complexes and Fc receptors of different cells (lymphocytes, macrophages of platelets) discriminated between cancer patients and health subjects and a high percentage (47-87%) of positivity was observed in such assays in patients with lung cancer. In contrast, none of the tests based on immune complex-complement interactions discriminated between cancer patients and health subjects. Immunochemical analyses of the PEG precipitates obtained from the sera tested revealed that the concentrations of IgG, IgA and C3 were significantly higher in the precipitates obtained from patients sera than from control sera, but no significant differences were seen in IgM and C1q concentrations. A 100% correct classification of individuals tested was obtained on discriminant analysis of results with 3 assays: EA rosette inhibition, ADCC inhibition and C3 concentration in PEG precipitates. Correlation between results obtained with individual sera by the different assays was very poor: significant correlation coefficients were found in only 13% of all possible paired comparisons. Our results suggest that Fc receptor-dependent assays are more suitable for detection and measurement of circulating immune complexes in lung cancer than tests based on interactions with complement.

Antigen density on the surface of mononuclear cells in SLE.

Searching for the cause of the known immunological abnormalities in systemic lupus erythematosus (SLE), the density of cell surface antigens was measured after immunofluorescent staining in a cell sorter. The densities of CD3, CD4, CD5, CD8 and sIgM lymphocyte antigens were the same on patients' lymphocytes as on lymphocytes from healthy subjects. The intensity of HLA-DR immunofluorescence was found to be decreased on patients' monocytes, while the expression of HLA-DR on lymphocytes of patients with SLE hardly differed from that in healthy subjects. Pretreatment of normal mononuclear cells with patients' sera free from immune complexes decreased the binding of anti-HLA-DR antibody to normal monocytes, but it hardly caused alteration on lymphocytes. After culturing, the expression of HLA-DR antigen on patients' monocytes became the same as on normal cells. A causal role of anti-HLA-DR autoantibodies is suggested and discussed.

Studies on the lymphocyte subpopulation in systemic lupus erythematosus by monoclonal antibodies.

T cells and T-cell subsets were studied with monoclonal antibodies in 15 patients with systemic lupus erythematosus (SLE) during a 6-wk period. During active states of disease, all investigated T-cell subsets decreased, but the reduction of suppressor cells seemed to be more pronounced, therefore the helper/suppressor ratio increased. Less suppressor cells could be detected during clinical impairments and more during improvements.