Anti-single Stranded DNA Antibodies Research Articles

Prozone-like phenomenon found in chemiluminescent enzyme immunoassay using magnetic particles for measurement of serum anti-single stranded DNA antibody titers: Definition and management

BackgroundSerum anti-single stranded DNA antibody (anti-ssDNAab) is used as a marker for systemic lupus erythematosus. We found a ‘prozone-like phenomenon,’ which was different from an original prozone phenomenon, in chemiluminescent enzyme immunoassay using magnetic particles for the measurement of serum anti-ssDNAab titers. We investigated mechanisms of the prozone-like phenomenon and countermeasures to prevent it from being overlooked. MethodsThis study examined 679 samples from patients tested for anti-ssDNAab titer at our hospital. In addition, the BF photometry OD value 2 (OD2), an index of optical density, was monitored simultaneously. ResultsThe undiluted samples with a prozone-like phenomenon showed extremely lower OD2. Those samples were able to be distinguished from other samples by setting OD2 criteria based on the 95% prediction interval. Significant differences (p < 0.05) were found in the titer ratios (ten-fold diluted against undiluted) between groups with >1.5 and other groups with <1.5 for the ratios of OD2. ConclusionsWe proposed two valuable methods to find a prozone-like phenomenon: one by setting OD2 criteria based on the 95% prediction interval and the other by analyzing the ratios both in titers and OD2 between undiluted and 10-fold diluted samples.

Serological and molecular analysis of parvovirus B19 infection in Mayan women with systemic lupus erythematosus in Mexico.

Background: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that mainly affects women, characterized by the production of autoantibodies. Its causal agent is unknown, but the combination of environmental, hormonal and genetic factors may favor the development of the disease. Parvovirus B19 has been associated with the development of SLE, since it induces the production of anti-single stranded DNA antibodies. It is unknown whether PV-B19 infection is an environmental factor that trigger or reactivate SLE in the Mexican Mayan population. Aim: A preliminary serological and molecular study of PV-B19 infection in Mayan women with established SLE was done. Methods: IgG and IgM anti PV-B19 were evaluated in 66 SLE patients and 66 control subjects, all women of Mayan origin. Viral DNA and viral load were analyzed by qPCR. Results: Insignificant levels of IgM were observed in 14.3% (4/28) of the patients and 11.4% (4/35) of control subjects. IgG was detected in 82.1% (23/28) of the patients and 82.9% (29/35) of control subjects, but were significantly higher in patients. Viral DNA was found in 86.0% (57/66) of the patients and 81.0% (54/66) of control subjects. Viral load, quantified in 28/66 patients and 31/66 controls which were positive for IgM and IgG, was significantly higher in controls. Conclusion: The high prevalence of PV-B19 in Yucatan, and the presence of IgM, IgG, and viral load in Mayan women with established SLE suggest that PV-B19 infection could be an environmental factor to trigger or reactivate SLE.

Clinical and magnetic resonance imaging features of multiple sclerosis with autoreactive antibodies in Ishikawa Prefecture, Japan

Previous reports of multiple sclerosis (MS) with autoantibodies might include neuromyelitis optica (NMO). We investigated the frequency of autoreactive antibodies (AR) in both MS and NMO. Systemic lupus erythematosus (SLE)-associated autoantibodies such as anti-Sm antibodies, anti-single stranded DNA antibodies and lupus anticoagulants were only identified in MS, whereas SLE itself is more commonly associated with NMO. Moreover, when magnetic resonance imaging features between autoreactive antibody-positive (AR(+))MS and -negative (AR(−))MS were compared, AR(+)MS cases showed significantly fewer than 3 periventricular lesions compared to AR(−)MS cases. These results may indicate different pathogenetic mechanisms underlying AR(+)MS and AR(−)MS.

Neutrophil Gelatinase Associated Lipocalin (NGAL) deficiency accelerates the onset of serum autoantibodies in pristane induced lupus (60.10)

Abstract NGAL (lipocalin-2), a member of the lipocalin superfamily, is expressed by neutrophils, hepatocytes, and renal resident cells following ischemia or inflammatory conditions &amp; is involved in innate immune responses during infection. However, its role in adaptive immunity has not been described. Previously, we had found that NGAL is instrumental in the pathogenesis of antibody mediated nephritis. To investigate a possible role for NGAL in the generation of autoreactive antibody responses, we examined its effect in an experimental lupus model. We injected pristane (0.5 ml per mouse i.p.) into wild type B6 (n=10) and NGAL-deficient (NGAL-/-) (n=10) mice and followed the course of disease. Analyzing the levels of serum autoantibodies at 3 months post injection, NGAL-/- mice had significant increases in IgG2a (p=0.007) and IgG2b (p=0.019) anti-double stranded DNA antibodies, and IgG2a (p=0.002) &amp; IgG2b (p=0.010) anti-single stranded DNA antibodies, and IgG anti-histone antibodies (p=0.025) as compared to pristane challenged, NGAL sufficient mice. Immunoprecipitation studies showed elevated serum anti-Sm/RNP antibodies in NGAL-/- mice compared to the WT mice at 3 months post injection, with an increase in titer and epitope diversity of this response at 6 months post injection. In conclusion, NGAL delays the onset of anti-nuclear antibodies in pristane induced lupus. The mechanisms by which NGAL plays a protective role in humoral autoimmunity are under investigation.

High concomitance of disease marker autoantibodies in anti-DFS70/LEDGF autoantibody–positive patients with autoimmune rheumatic disease

Autoantibodies against dense fine speckles 70 (DFS70) are found in 10% of healthy individuals, but only in a tiny population of patients with autoimmune rheumatic disease. The antibody may thus be a marker of autoimmune rheumatic disease negativity. To investigate this possibility, we examined the presence of various disease-marker autoantibodies in anti-DFS70 antibody-positive patients with autoimmune rheumatic disease. Serum samples from 500 patients with various types of autoimmune rheumatic disease were examined for anti-DFS70 antibodies by indirect immunofluorescence and immunoblotting. Various disease-marker autoantibodies were measured by enzyme-linked immunosorbent assay. Twenty-two patients were positive for anti-DFS70 antibodies. Eighteen patients also had disease-marker autoantibodies including anti-double stranded DNA, anti-cardiolipin, anti-SS-A, or other antibodies. In one patient with Sjögren syndrome and two patients with dermatomyositis, no disease-marker antibodies were found; however, one patient with dermatomyositis had a concomitant anti-cytoplasmic antibody. All seven systemic lupus erythematosus patients fulfilled the classification criteria for this disease even if anti-nuclear antibody-positive findings were excluded. One patient with morphea had high-titer anti-single stranded DNA antibody. According to this and previous studies, patients with only anti-DFS70 antibody are rarely diagnosed as having autoimmune rheumatic disease. Recognizing dense fine speckle patterns in anti-nuclear antibodies tests is, thus, very important for analysis of laboratory results in rheumatology clinics.

A novel dual staining method for identification of apoptotic cells reveals a modest apoptotic response in infarcted mouse myocardium

Confocal scanning laser microscopy was used to investigate the myocardium of control C57BL/6 and plasminogen activator inhibitor 1 knockout (PAI-1KO) mice 3 days following persistent ligation of the left descending coronary artery. Paraffin sections taken from infarcted areas of the left ventricle were stained with antibodies recognizing cardiomyocytes, neutrophils, macrophages and apoptotic cells. In both animal groups, a strong neutrophil response was noted in the infarcted myocardium, with a large proportion of these cells also displaying staining for anti-alpha-sarcomeric actin in the PAI-1KO animals. Abundant macrophages were also identified in the infarcted regions of both animal groups, forming demonstrable streams at the border region in the C57BL/6 control animals. Surprisingly, only sparse cells from both animal groups were labeled with the apoptotic markers anti-cleaved caspase 3 antibody and anti-single stranded DNA antibody (following formamide treatment). A dual immunostaining protocol was developed to localize both of these apoptotic markers in the same cell. Again, only scattered cells were found displaying both markers in the zones of infarction, suggesting that 3 days of persistent ischemia results in a robust necrotic response, but only a very minor apoptotic response in this mouse model.

Anti‐agalactosyl immunoglobulin G antibodies in localized scleroderma

Anti-agalactosyl immunoglobulin G (IgG) antibodies (anti-AG IgG) have been reported to be detected and correlated with disease activity in some collagen diseases. Forty-seven serum samples from patients with localized scleroderma were examined using an enzyme-linked immunosorbent assay. Anti-AG IgG were positive in 19% of patients with localized scleroderma. The frequency of anti-AG IgG in generalized morphea was much higher than that in linear scleroderma or that in morphea. There was a significant correlation between anti-AG IgG levels and the number of the sclerotic lesions and between anti-AG IgG levels and the number of involved areas. The levels of anti-AG IgG were significantly higher in patients with antinuclear antibody, antisingle-stranded DNA antibody or rheumatoid factor than in those without. Anti-AG IgG can be an indicator of the severity of localized scleroderma.

Serum thymic factor prevents LPS-induced pancreatic cell damage in mice via up-regulation of Bcl-2 expression in pancreas.

The protective effect of synthetic serum thymic factor (FTS) nonapeptide on lipopolysaccharide (LPS)-induced pancreatic cell damage in 10-week-old BALB/c male mice was investigated. Mice were divided into three groups. Group I was treated with LPS (10 micro g/head; i.p.) (LPS-treated mice). Group II was administered with FTS (50 micro g/head; i.p.) 24 hr before treatment with LPS and complemented immediately before LPS injection with FTS (50 micro g/head; i.p.) (FTS-administered mice). Group III was only treated with the same volume of saline (control mice). Treatment of LPS in vivo resulted in the destruction of pancreatic acinar cells. In those cells, many apoptotic cells were detected by immunohistochemistry using an anti-single stranded DNA antibody. Immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) revealed that LPS treatment also caused low or a lack of insulin expression in pancreatic islets. In contrast, morphological change was not seen and apoptotic cell death was suppressed in pancreatic cells of FTS-administered mice. Moreover, insulin expression was normal in those mice. FTS administration enhanced expression of Bcl-2 mRNA levels in pancreatic tissues and IL-6 mRNA levels in splenocytes significantly compared with those of LPS treatment at 3 hr after LPS injection. These findings suggest that FTS prevents LPS-induced cell damage via enhancing Bcl-2 expression in the pancreas and systemic IL-6 production.

Change in apoptosis in the gastric surface epithelium and glands after eradication of Helicobacter pylori

Background. Change in apoptosis in gastric glands after eradication of Helicobacter pylori has never been reported. Aims. The purpose of this paper is to investigate the change in apoptosis in gastric glands after eradication of Heliobacter pylori. Patients and methods. We studied 23 Heliobacter pylori-positive patients with duodenal and gastric ulcers, who were monitored for 6–12 months after eradication, and eight controls. Biopsies were taken from the antrum and body. Apoptosis was evaluated immunohistochemically using anti-single stranded DNA antibody. Apoptotic index was calculated by counting immunostained cells in surface epithelial and glandular cells. Results. In the surface epithelium, Apoptotic indexes were significantly higher in patients than in controls. In the upper portion of fundic glands, apoptotic indexes were significantly higher in patients with gastric ulcers (14.2% (9.3, 17.8)) (median (1st quartile, 3rd quartile)) than in controls (8.0% (2.0, 9.0), p<0.01) and decreased significantly after eradication (3.4% (2.0, 5.3)), p<0.01). In pyloric glands, apoptotic indexes were no different between patients and controls. In the lower portion of fundic glands, apoptotic indexes were very low, both in patients and in controls. Conclusions. Our results showed that apoptosis, not only of surface epithelial cells but also of glandular cells in the upper portion of fundic glands, increased in Heliobacter pylori-positive patients with gastric ulcers and decreased to normal levels after eradication of Heliobacter pylori.

E. Thyroglobulin (Tg) Measurement

ThyroidVol. 13, No. 1 Section 3: Thyroid Tests for the Clinical Biochemist and PhysicianE. Thyroglobulin (Tg) MeasurementPublished Online:9 Jul 2004https://doi.org/10.1089/105072503321087033AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byProzone-like phenomenon found in chemiluminescent enzyme immunoassay using magnetic particles for measurement of serum anti-single stranded DNA antibody titers: Definition and managementClinica Chimica Acta, Vol. 485Sequential Changes of Serum Antithyroglobulin Antibody Levels Are a Good Predictor of Disease Activity in Thyroglobulin-Negative Patients with Papillary Thyroid Carcinoma Ching-Jung Hsieh and Pei-Wen Wang7 March 2014 | Thyroid, Vol. 24, No. 3Changes in TNM stage, reoperation and 131-I ablation rate during the use of newer methods for the preoperative diagnosis of differentiated thyroid carcinoma4 January 2012 | Clinical Endocrinology, Vol. 76, No. 2Differences in serum thyroglobulin measurements by 3 commercial immunoradiometric assay kits and laboratory standardization using Certified Reference Material 457 (CRM-457)22 December 2009 | Head & Neck, Vol. 32, No. 9Serum Basal Thyroglobulin Measured by a Second-Generation Assay Correlates with the Recombinant Human Thyrotropin–Stimulated Thyroglobulin Response in Patients Treated for Differentiated Thyroid Cancer Carole Spencer, Shireen Fatemi, Peter Singer, John Nicoloff, and Jonathan LoPresti16 June 2010 | Thyroid, Vol. 20, No. 6Thyroglobulin Measurement6 April 2010Thyroglobulin as a marker of iodine nutrition status in the general populationEuropean Journal of Endocrinology, Vol. 161, No. 3Technology Insight: measuring thyroglobulin and thyroglobulin autoantibody in patients with differentiated thyroid cancer12 February 2008 | Nature Clinical Practice Endocrinology & Metabolism, Vol. 4, No. 4Intense 18-fluorodeoxyglucose uptake by the thymus on PET scan does not necessarily herald recurrence of thyroid carcinoma18 March 2014 | Journal of Endocrinological Investigation, Vol. 28, No. 2Thyroglobulin Autoantibody Levels Below the Cut-Off for Positivity Can Interfere with Thyroglobulin Measurement J. M. Cubero, J. Rodríguez-Espinosa, C. Gelpi, M. Estorch, and R. Corcoy9 July 2004 | Thyroid, Vol. 13, No. 7Thyroglobulin Volume 13Issue 1Jan 2003 To cite this article:E. Thyroglobulin (Tg) Measurement.Thyroid.Jan 2003.57-67.http://doi.org/10.1089/105072503321087033Published in Volume: 13 Issue 1: July 9, 2004PDF download

Investigation of the mechanism of drug-induced autoimmune hemolytic anemia in cynomolgus monkeys elicited by a repeated-dose of a humanized monoclonal antibody drug.

We investigated the mechanism of hemolytic anemia detected in a repeated-dose toxicity study using cynomolgus monkeys that were treated with a humanized antibody drug. This drug was an IgG1 monoclonal antibody (MoAb) that binds to the human HM1.24 antigen named anti-HM1.24 MoAb. The presence of the HM1.24 antigen on the erythrocyte membranes and the erythrocyte agglutination following the addition of anti-HM1.24 MoAb was examined. In addition, an indirect Coombs' test, a hemolysis assay and the measurement of anti-single stranded-DNA antibodies were performed using test animal serum or plasma. The specific binding of FITC- and 125I-labeled anti-HM1.24 MoAb to the erythrocyte membrane was not observed. HM1.24 antigen was not identified on the erythrocyte membranes. However, a high concentration (more than 713 microg/mL) of anti-HM1.24 MoAb hemagglutinated the erythrocyte suspensions. The cause of this agglutination was unclear, but it is assumed that the non-specific binding and/or adhesion caused the direct agglutination. In the examination using test serum from the anemic monkeys, a positive reaction in the indirect Coombs' test was noted. Moreover, in these Coombs' test-positive animals, the production of anti-single stranded-DNA antibodies was sequentially increased. In the female monkey sacrificed in extremis due to severe anemia, an in vitro hemolytic reaction was detected attributable to complement activation. From these results, the hemolytic anemia detected in the repeated-dose toxicity study was diagnosed as a drug-induced autoimmune hemolytic anemia (AIHA) and the primary cause was assumed to be production of IgG class anti-erythrocyte autoantibodies.

Time-Dependent Autoimmune Response of Dichloroacetyl Chloride in Female MRL +/+ MICE

Welders are exposed to dichloroacetyl chloride (DCAC) when trichloroethene (TCE) is used as a degreasing agent. Human exposure to TCE and tetrachloroethane can also lead to formation of DCAC in situ through metabolism. Due to its strong acylating property, it can bind with cellular macromolecules and act as hapten and consequently may elicit autoimmune (Al) response. Earlier, we reported that both TCE and DCAC induce/accelerate Al response in MRL +/+ mice, and DCAC even at 50 fold lower concentration induced greater Al responses. These studies, however, were conducted at a single time point (six weeks of treatment) and therefore necessitate a time-dependent characterization of this DCAC-induced Al response. Female MRL + /+ were given ip treatments of 0.2 mmol/kg DCAC in 100 μl of corn oil every 4th day, while controls received an equal volume of corn oil only. DCAC treatment resulted in spleen weight increases at all time points whereas serum IgG showed significant increases at 4, 6 and 8 weeks of treatment. Serum autoantibodies, i.e., anti-nuclear antibodies, anti-single stranded DNA antibodies and anti-cardiolipin antibodies showed positive responses only after 4 weeks of treatment. However, the optimal responses were observed at 6 weeks and subsequently the responses diminished (at 8 weeks). The DCAC-specific antibodies showed a pattern similar to autoantibodies, i.e., an optimal response at 6 weeks of treatment. Our results thus suggest that DCAC under the current experimental conditions induces an optimal Al response at 6 weeks of treatment and further emphasize the usefulness of MRL +/ + mice in studying chemical-induced autoimmunity.

Detection of polyanion-restricted anti-histone antibodies in patients with systemic lupus erythematosus.

The nature of the antibodies responsible for lupus erythematosus (LE) cells in systemic lupus erythematosus (SLE) remains obscure. We examined whether polyanion-restricted anti-histone antibodies were present in serum of patients with SLE using Western blotting analysis. Dextran sulfate or alginate was used as a polyanion compound in place of DNA. Antibodies which recognized dextran sulfate-histone complexes were present in serum of patients with SLE (17/34, 50%). These antibodies were detected in most SLE patients positive for LE cells (17/18, 94%) but not in those negative for LE cells or in patients with other collagen diseases. Similar results were obtained using alginate-histone complexes as antigens for Western blotting analysis. The antibodies to dextran sulfate-histone or alginate-histone complexes in serum of SLE patients were completely absorbed by treatment of serum with DNA-histone complexes, while they were unaffected by treatment with DNA only. The presence of antibodies to free histones and dextran sulfate-histone complexes did not seem to be related to the titer of anti-single stranded DNA antibody and anti-double stranded DNA antibody. We demonstrated the presence of polyanion-restricted antibodies in SLE, which may be responsible for the LE factor.

Serum concentration of procollagen type I carboxyterminal propeptide in localized scleroderma

<h3>Background and Design:</h3> Recently, we reported that the serum procollagen type I carboxyterminal propeptide (P1CP) level of patients with systemic sclerosis was elevated and correlated with disease severity. In this study, the serum level of P1CP was measured using the enzymelinked immunosorbent assay in 39 patients with localized scleroderma and in 30 control subjects. <h3>Results:</h3> The mean P1CP level in the patients was significantly higher than that in the normal control subjects. In 30% of the patients with localized scleroderma, the serum P1CP level was considered to be elevated (&gt;305 ng/mL; ie, 2 SDs above the mean control value). The mean serum P1CP level in the patients with generalized morphea was significantly higher than in the pa- tients with morphea or linear scleroderma. In addition, the serum P1CP level in the patients with localized scleroderma was correlated with the number of sclerotic lesions, and it was negatively correlated with the duration of the disease. Anti—single-stranded DNA antibody and antihistone antibody were detected significantly more frequently in the patients with elevated P1CP than in the patients with normal P1CP. <h3>Conclusion:</h3> These findings suggest that the serum P1CP level is a useful indicator of disease severity in patients with localized scleroderma, as it has been found to be in those with systemic sclerosis. (Arch Dermatol. 1994;130:1269-1272)

The Relationship Between Discoid and Systemic Lupus Erythematosus

PREVIOUS RESEARCH on cutaneous lupus erythematosus lesions has been directed at examining the relationship between the scarring lesions of discoid lupus erythematosus (DLE) and systemic lupus erythematosus (SLE) and the pathogenesis of the lesions of cutaneous lupus erythematosus. The lesions of DLE generally occur as scarring isolated cutaneous lesions in the absence of systemic features. However, studies of large populations of patients with SLE indicate that approximately 15% to 20% of patients with SLE (satisfying the American College of Rheumatology criteria for SLE) also possess discoid lupus lesions. 1 In addition, it has been recognized that over time approximately 5% to 10% of patients with DLE will develop clinical features that satisfy the American College of Rheumatology diagnosis of SLE. Previous studies by Kulick et al 2 have indicated that approximately 25% of patients with DLE possess anti—single-stranded DNA antibodies of the IgM isotype. Furthermore, Callen et al 3 have

Detection of anti-double and anti-single stranded DNA antibodies in chronic liver disease: significance of anti-double stranded DNA antibody in autoimmune hepatitis.

Anti-DNA antibodies were determined by an enzyme-linked immunosorbent assay in 116 patients with chronic liver disease consisting of 21 cases of autoimmune hepatitis (AIH), 17 of primary biliary cirrhosis (PBC), and 78 of non-autoimmune-type of chronic liver disease. The assay was also performed on 83 patients with collagen disease, as a control group. Anti-double stranded DNA antibody (anti-dsDNA) was detected in 10/21 (48%) of the AIH patients and in 3/17 (17%) of the PBC patients, but not in those with other liver diseases. In contrast, anti-single stranded DNA antibody (anti-ssDNA) was positive not only in AIH and PBC, but also in those with non-autoimmune-types of chronic liver disease. Follow-up liver histology disclosed that the 2 patients with AIH who were positive for anti-dsDNA developed liver cirrhosis, whereas the 4 patients who were negative for anti-dsDNA, and those who showed a disappearance of anti-dsDNA following corticosteroid therapy, improved from chronic active to chronic persistent hepatitis.

Adoptive transfer of the gld syndrome in double congenic nude lpr mice.

Homozygosity for either the lymphoproliferation (lpr) or the generalized lymphoproliferative disease (gld) mutation of mice causes the development of strikingly similar autoimmune and lymphoproliferative syndromes. The relationship between the lpr and gld mutations was studied by grafting B6 gld spleen cells (SC) to athymic B6 nude lpr mice (B6 nulpr) or to B6 nude (B6 nu) mice as controls. The injection of B6 gld SC, but not of B6 wild SC, to B6 nulpr mice caused a prolongation of survival of the short living B6 nulpr recipients. This was associated with elevated anti-single stranded DNA antibody titers and a serum hyperglobulinemia, as well as by a splenomegaly which was nearly as high as in genetically B6 gld mice, and by a marked lymphadenopathy (though milder than that of B6 gld mice). In contrast the [gld----nu] chimaeras showed a more attenuated form of gld-induced syndrome. These results suggest that the lpr environment supplied in athymic lpr recipients is compatible with--and may even favour--the development of the gld-induced syndrome.

Prevalence and Characteristics of Anti—Single-Stranded DNA Antibodies in Localized Scleroderma

Prevalence, levels, and immunoglobulin classes of anti-single-stranded DNA antibodies were determined by an enzyme-linked immunosorbent assay in 52 patients with localized scleroderma (33 with morphea, four with generalized morphea, and 15 with linear scleroderma), in 60 healthy controls, and, for comparison, in 31 patients with systemic lupus erythematosus. Localized scleroderma revealed a significant prevalence of anti-single-stranded DNA antibodies, mainly characterized by high levels and IgM and IgA isotypes. Comparison of antibody characteristics in different clinical forms of localized scleroderma showed some significant differences (levels and immunoglobulin isotypes). Comparison with systemic lupus erythematosus showed that frequency, high levels, and IgG isotype of anti-single-stranded DNA antibodies significantly prevailed in systemic lupus erythematosus, while the IgM isotype significantly prevailed in localized scleroderma. However, generalized morphea and linear scleroderma did not significantly differ from systemic lupus erythematosus as regards antibody frequency and prevalence of high antibody levels.

Effects of Short-term Administration of Antipsychotic Drugs on Lymphocyte Subsets in Schizophrenic Patients

To the Editor.— Studies of various immunological parameters in schizophrenic patients are potentially confounded by the possible effects of neuroleptic medication on the immune system. Certain neuroleptic drugs, including the phenothiazines, chlorpromazine, and thioridizine, have been associated with the development of antinuclear-and and anti—single-stranded DNA antibodies, elevated serum rheumatoid factor, and even splenomegaly.1Clozapine, a dibenzodiazepine derivative, has been reported to produce a potentially lethal agranulocytosis in a small percentage of patients,2,3and therefore may have direct effects on hematopoiesis. In this issue of theArchives, we demonstrate that a subgroup of schizophrenic patients (approximately 30%) have elevated numbers of CD5+(Leu1) B lymphocytes.4This subset of B lymphocytes has been shown by several laboratories to be elevated in patients with certain autoimmune disorders.5-7The CD5+B lymphocytes are known to spontaneously proliferate in vitro8and preferentially produce autoantibodies.5,9,10In our study,4schizophrenic

Bone marrow cells from young and old New Zealand Black mice can reconstitute B lymphocytes in Severe Combined Immunodeficient recipients

The formation of B lymphocytes in young New Zealand Black (NZB) mice proceeds at an accelerated rate, resulting in a deficiency of B lineage progenitors in mice of 15 weeks of age and older. Multiple studies have indicated that intrinsic defects in B lineage cells as well as in the hemopoietic microenvironment in which they develop contribute to these cellular abnormalities. To determine whether the B-cell hyperactivity observed in young mice could be observed in a normal environment, bone marrow cells from young (4 weeks or less) NZB donors were transplanted into Severe Combined Immunodeficient (SCID) mice that have a marked deficiency of lymphocytes but an apparently normal hemopoietic microenvironment. Engraftment of donor lymphoid cells can occur without pretransplant conditioning regimens, thus minimizing the chances of transferring microenvironmental elements. Marrow from young NZB donors reconstituted surface IgM-expressing B cells and CFU-B (B-cell colony-forming unit) in the marrow of SCID mouse recipients to levels comparable to that observed with donor NZB.xid marrow. The latter mice carry the xid gene that ameliorates the defects exhibited by B lineage cells of NZB mice. Both the number of surface IgM-expressing B cells and CFU-B were higher in the spleen of SCID mice that received NZB grafts than marrow cells from donor BALB c or NZB.xid mice. Marrow from young NZB donors also reconstituted Thy-1, L3T4 and Lyt2-expressing cells in the spleen to levels higher than observed with young NZB.xid donor cells. The transplantation of marrow from 6-month-old NZB donors made it possible to test whether B lineage cells were present in that tissue and could mediate reconstitution in the normal SCID environment. Marrow from old NZB donors did reconstitute B cells in the marrow and spleen of SCID recipients. The level of reconstitution was comparable to that mediated by young BALB c cells and twice that of old NZB.xid donor cells. The absolute number of splenic CFU-B was also higher in recipients of old NZB marrow as compared to young BALB c cells. Old NZB.xid donor marrow reconstituted splenic Thy-1, L3T4 and Lyt2 T cells to levels less than observed with NZB donor cells. Analysis of serum Ig in recipients of old NZB cells indicated higher levels of total IgM as compared to mice engrafted with NZB.xid cells, and anti-single stranded DNA antibodies were detected.