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PubMedDate not supplied

[Immunological diagnosis of hilarmediastinal lymphadenopathies (author's transl)].

In the last few years, we have adopted the following immunological techniques for the study of hilarmediastinal lymphadenopathies: the E and EAC rosette tests (composition of the lymphocyte population) for an evaluation of the general immunological picture, the delayed-type cutaneous tests to reveal the specific picture of cell-mediated immune responses, and the leucocyte migration inhibition test against related and unrelated antigens. This cellular technique was integrated with the determination of precipitating and agglutinating antibodies against the same antigens. Data are reported regarding tubercular and sarcoid lymphadenopathies, Hodgkin's disease, and secondary neoplastic lymphadenopathy with prevalent intratoracic localization. The techniques used demonstrated that tubercular lymphadenopathy is associated with a well defined immunological profile which is both humoral and cellular. Sarcoid lymphadenopathy (thoracic sarcoidosis) showed a specific, well characterized immunological picture as regards cell-mediated immune responses. In Hodgkin's disease (hilarmediastinal lymphadenopathy) the immunological technique showed up a general, depressed immunological picture, particularly as regards the cell-mediated immunitary response, presumably partly due to the treatment given (physical and pharmacological therapy). Secondary neoplastic lymphadenopathy showed a similar pattern, as far as the immunological parameters used until now are concerned. On the basis of experience gained to date, we believe that the immunological techniques can make a contribution to diagnostic and clinical studies of tubercular and sarcoid lymphadenopathies.

Antibody Formation↗
PubMed1996

[Immunologic tests in patients with idiopathic uveitis--preliminary reports].

AIM: This study aimed to evaluate the immune system function in patients with uveitis of unknown aetiology. METHODS: The clinical material comprised 19 patients with endogenous uveitis. In all cases the following immunological tests were performed: serum immunoglobulins A, G, M, total IgE, circulating immune complexes, complement components C3c and C4-all determined by laser nephelometry; antinuclear antibodies assessed with indirect immunofluorescence method using HEp-2 cell lines; and antineutrophil cytoplasmic antibodies using indirect immunofluorescence test. In 4 cases lupus anticoagulant was measured with APTT and dRVVT assays. RESULTS: Among our 19 examined patients immunological abnormalities were found in 12 cases. Changes in immunoglobulin concentrations were found in 8 cases. In 4 patients abnormalities of the complement system were observed. Antinuclear antibodies with speckled pattern in indirect immunofluorescence were present in 7 cases. CONCLUSION: In a proportion of patients with endogenous uveitis mild immunological abnormalities were present, suggesting an autoimmune background of the disease. Studies of the immunological profile can therefore help in better evaluation of the patients. It remains to be determined whether the observed immunological alterations are of any importance in the pathogenesis of the studied disease.

Adolescent↗
PubMed2006

Analysis of the cytokine profile in spleen cells from dogs naturally infected by Leishmania chagasi.

Recent studies suggest that asymptomatic dogs infected with canine visceral leishmaniasis (CVL) develop a Th1 immunological profile whilst oligosymptomatic and symptomatic CVL-infected animals present a Th2 profile. In the present study, an RT-PCR method has been standardised and employed to evaluate the frequency and the semi-quantitative level of expression of the cytokines IL-4, IL-10, IL-12, INF-gamma and TNF-alpha in splenocytes of 30 dogs naturally infected with Leishmania chagasi and of 7 non-infected dogs (NID). An increase in the level of expression of IL-12 (p=0.059) was detected in all CVL-infected dogs compared with NID. In dogs exhibiting high parasitism, the frequency of expression of IL-10 was higher (p=0.011) than in animals presenting low parasitism or medium parasitism (MP) and in NID animals, whilst the level of expression of IL-10 was higher (p=0.0094) than in animals exhibiting MP and in the NID group. Positive correlations between the levels of expression of IL-10 with respect to the progression of the disease (IL-10: r=0.3510; p=0.0337) and the levels of expression of IL-10 and INF-gamma increase in parasitism (IL-10: r=0.3428; p=0.0438 and INF-gamma: r=0.4690; p=0.0045) were observed. Such data suggest that CVL is marked by a balanced production of Th1 and Th2 cytokines, with a predominant accumulation of IL-10 as a consequence of an increase in parasitic load and progression of the disease, and INF-gamma was related with the increase in parasitic load.

Animals↗
PubMed2004

[Nuclear auto-antibodies: a useful tool for the diagnosis, the classification and the prognosis of systemic sclerosis].

PURPOSE: Systemic sclerosis (SSc) like other connective tissue diseases is characterized by the occurrence of antinuclear auto-antibodies (ANA). We reviewed the diagnostic value and prognostic value of ANA in SSc. CURRENT KNOWLEDGE AND KEY POINTS: LeRoy proposed new criteria of limited forms of SSc which take into account the immunological profile of the patients. Anticentromere, antitopoisomerase I, antifibrillarin, anti-PM-Scl, antifibrillin or anti-RNA-polymerase I or III are considered as specific anti-autobodies. Whereas anticentromere antibodies are more associated with limited SSc and antitopoisomerase I with diffuse SSc, other auto-antibodies were associated with other organ involvement : anti-RNA-polymerase I or III and renal crisis, anti-U1-RNP and pulmonary hypertension and pulmonary fibrosis, etc. Patient with persistent antitopoisomerase I antibodies have a poor survival, those with antitopoisomerase antibodies that disappear with time have a better prognosis. FUTURE PROSPECTS AND PROJECTS: A better identification of the patients with SSc, an individual biological profile and organ involvement may help better management of the disease and better access to clinical trials. The development of new immunological tests and their clinical application should help us in that way.

Antibodies, Antinuclear↗
PubMed2001

TINU syndrome associated with reduced complement levels.

The TINU syndrome (tubulointerstitial nephritis and uveitis) was first described by Dobrin et al. in 1975. Since then, more than 50 cases have been documented each with diverse immunopathogenetic and genetic characteristics. The aim of this report is to describe a case of TINU associated with reduced complement levels. We profile a 48-year-old white female with persistently reduced C4 complement levels during the acute phase of the pathology and with an unaltered immunologic profile. Renal biopsy evidenced a significant lymphocytic interstitial infiltration. Immunohistochemical studies of the interstitium infiltrates was positive for the presence of the T (CD3) markers (CD4 > CD8). Steroid therapy yielded a complete regression of the symptomatology with normalization of the complement levels. We suggest that it is possible to hypothesize that the various immunologic alterations associated with TINU, including the transient reduction complement levels, may be secondary to multiple inflammatory mechanisms which express themselves throughout the pathology.

Acute-Phase Reaction↗
PubMedDate not supplied

Serum immunoglobulins, IL-1beta, IL-2, and IFN-gamma gamma level in patients with lymphedema treated with ortho-beta-hydroxy-ethyl rutosides (HR).

BACKGROUND: This investigation was undertaken to study the clinical characteristics and the humoral immune pattern in lymphedema patients undergoing O-beta-hydroxy-ethyl rutoside therapy. METHODS: A complete physical examination was performed on 27 lymphedema patients (postmastectomy and postphlebitis) and 17 healthy controls. Clinical evaluation of affected limbs was carried out concerning swelling, circumference, mobility, and tissue tension, while immunologic studies consisted of serum IgG, IgA, IgM, C3, and 1-glycoprotein, interleukin-1 beta, interleukin-2, and IFN-gamma levels. Immunoglobulins and alpha-1-acid glycoprotein were assessed by radial immune diffusion (RID) and interleukin levels, by ELISA (R & D Systems Kits, R & D Systems, Minneapolis, MN, USA). On admission, patients received O-beta-hydroxy-ethyl rutosides (HR) 1 g/day during a period of 6 months. RESULTS: These demonstrated several clinical, functional, and immunologic alterations in lymphedema patients. HR treatment produced a remarkable reduction in swelling, circumference, and tissue tension, and an improvement in mobility. In addition, edema was also diminished. The immunologic profile observed in untreated lymphedema patients is as follows: IgG and alpha-1-acid glycoprotein concentration were slightly diminished in comparison with the control group, reaching normal levels after therapy. The difference among these values was significant (p <0.001). Contrariwise, normal C3 values were detected with a significant posttreatment decrease (p <0.001). Normal serum IgA and IgM levels in patients with lymphedema before and after HR treatment are shown, and are similar to those of the control group. In addition, Il-1beta and IL-2 values are higher in relation to control values (p <0.01), attaining normal concentration after therapy. Normal levels of IFN-gamma were found in lymphedema patients, and there was no difference with control values. The concentration of this cytokine was not influenced by HR. IL-1beta and IL-2 concentrations were higher than in controls (p <0.001). Values reached normal levels after therapy (p <0.01). CONCLUSIONS: Diverse clinical and immunologic alterations were evidenced in lymphedema patients. The immunoglobulin profile and IL-1beta and IL-2 levels were also modified. After HR treatment, their improvement was reflected by the favorable effect regarding the previously mentioned alterations. O-beta-hydroxy-ethyl rutosides are effective both clinically and immunologically.

Adult↗
PubMed1999

Assessment of splenic functions in patients with hepato-splenic schistosomiasis using non-invasive techniques.

This study was carried out on forty cases, classified into 3 groups; group I: 10 healthy controls subjects, group II: 20 patients with hepatosplenic schistosomiasis and group III: 10 bilharzial patients who underwent total splenectomy. All cases were subjected to clinical examination, abdominal ultrasonography, rectal snips and laboratory investigations which included: stool and urine analysis, complete blood picture, IHAT for bilharziasis, liver function tests, viral markers, estimaton of T-lymphocyte subpopulations (CD(+)3, CD(+)4, & CD(+)8) by flow Cytometry, silver stained blood films to detect argyrophilic inclusions and 99mTc sulphur colloid splenic scan which was applied to group II only. The present results revealed varying degrees of hypersplenism (anaemia, leukopenia & thrombocytopenia) in GII. Seventy percent of this group was positive for HbsAg, HCV or both in association with schistosomiasis. Abnormal red blood cells (acanthocytes, target cells, pitted cells & normoblasts) and inclusion bodies (Howell Jolly bodies, argyrophilic inclusions & pappenhiemer bodies) were detected with different values in GIII. CD(+)4 cells were moderately reduced in GII while they were markedly decreased in GIII. CD(+)8 cells were elevated in GII and returned nearly to the normal values in GIII with decrease in number of total T-lymphocytes. Most patients of GII showed marked squestration of 99mTc labelled R.B.Cs. in the spleen with reversed hepatic/splenic ratio (normally hepatic/splenic ratio is over two). IHAT showed positivity in 90% of patients in GII while it was 50% in GIII. Although total splenectomy improved the haematological pattern and the cytopenias, which are prominent features in hepatosplenic schistosomiasis, yet the immunological profile was still altered. So, it is recommended to perform segmental splenectomy with retention of a normal mass of functioning residual spleen to preserve more immunological function and to protect against life-threatening occurrence of post-splenectomy sepsis.

Adult↗
PubMed2006

Protein kinase Cgamma autoimmunity in paraneoplastic cerebellar degeneration and non-small-cell lung cancer.

BACKGROUND: The clinical and immunological profiles of patients with paraneoplastic cerebellar degeneration (PCD) and non-small-cell lung cancer (NSCLC) are not well known. OBJECTIVE: To review the clinical and immunological features of patients with PCD, NSCLC and without well-characterised onconeural antibodies. METHODS: The clinical features of nine patients with the diagnosis of classical PCD and NSCLC, included in our archives, were retrospectively reviewed. The presence of antibodies to cerebellar components was determined by immunohistochemistry and immunoblot of rat cerebellum. A cDNA library of human cerebellum was screened with the positive sera to identify the antigen. RESULTS: Nine patients with PCD and NSCLC were identified. Six patients were men, and the median age at diagnosis of PCD was 63 (range 47-73) years. PCD was completely reversed in two patients, and partially in one, after treatment of the tumour. The serum of one of the patients with PCD showed a unique reactivity with Purkinje cells. The screening of a cerebellar-expression library resulted in the isolation of protein kinase Cgamma (PKCgamma). PKCgamma immunoreactivity was not observed in the serum of 170 patients with non-paraneoplastic neurological syndromes, 27 patients with PCD, no onconeural antibodies and small-cell lung cancer, and 52 patients with NSCLC without paraneoplastic neurological syndromes. The NSCLC from 11 patients without PCD did not express PKCgamma at either the RNA or protein level. However, many cells of the NSCLC of the patient with PKCgamma antibodies expressed PKCgamma. CONCLUSION: PCD occurs in patients with NSCLC without typical onconeural antibodies and is associated with immune reactions against key proteins of the Purkinje cells.

Aged↗
PubMed1987

[Expression of blood group antigens in 30 patients with transitional-cell carcinomas of the bladder].

From the follow up of 30 patients whose bladder tumours were repeatedly resected over a period ranging from several months to 18 years, we carried out a study of AGS Antigen expression using an A B O histokit. We were able to establish that this histokit is reliable and very easy to use. We also observed in the urothelial tumours a modification in AGS expression tending towards frequent loss. The AGS staining coincides with the grade of the tumour. Tumours totally stained are always of low grade. However, in this short group of patients, we were unable to draw any interesting correlation between the immunological profile and the clinical course of the transitional bladder carcinomas. In the case of patients with superficial tumours whose histological aspect and clinical course are comparable, the immunological aspect differs. It must be emphasised that in subsequent studies necessary to establish the prognosis of bladder tumours the A B O histokit is easy to use in conjunction with the histological study.

ABO Blood-Group System↗
PubMed1980

Hidden anti-nuclear antibodies in rheumatic diseases.

Hidden anti-nuclear antibodies are demonstrated by immunofluorescence using smears of rat nuclei as substrate and rat liver section technique when sera are incubated with penicillamine. The non-detection of hidden anti-nuclear antibodies by tissue sections in the absence of a splitting agent may be due to the formation of high molecular weight complexes between rheumatoid factors and anti-nuclear antibodies. These high molecular weight complexes containing anti-nuclear antibodies do not have access to tissue nuclear antigens, but can react directly with free nuclei. It is postulated that anti-nuclear antibodies may represent the early pathway of both rheumatoid arthritis and connective tissue diseases. The demonstration of hidden anti-nuclear antibodies in seropositive sera indicates that rheumatoid factors may have a protective effect. It may explain dissimilarities observed in the clinico-immunological profile of rheumatoid arthritis and systemic lupus erythematosus. The splitting effect of penicillamine observed in vitro may be similar in vivo. It can explain clinical improvement and immunological side effects observed in rheumatoid arthritis patients treated with this drug.

Antibodies, Antinuclear↗
PubMed2006

Mixed inflammatory/regulatory cytokine profile marked by simultaneous raise of interferon-gamma and interleukin-10 and low frequency of tumour necrosis factor-alpha(+) monocytes are hallmarks of active human visceral Leishmaniasis due to Leishmania chagasi infection.

Considering the complexity of the immunological events triggered during active visceral Leishmaniasis (VL), the relevance of the segregation of the immune response during human VL into type 1 and type 2 still remains unclear. For this purpose, in individuals living in risk areas for VL, we have evaluated especially asymptomatic individuals and patients with active VL, the plasmatic levels of cytokines and reactive nitrogen species under ex vivo conditions. In addition, we have also performed an analysis of intracellular cytokine patterns of circulating leucocytes after short-term culture, particularly in the absence of antigenic-specific stimulation, in order to reflect dynamic events of immune response in vivo during Leishmania chagasi infection. Although asymptomatic individuals and non-infected subjects presented a similar immunological profile, an outstanding inflammatory/regulatory profile, based on higher plasmatic levels of cytokines such as interleukin (IL)-8, interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, IL-6 and IL-10, was associated with clinical status observed in active VL. In this context, we hypothesize that IL-10, through its ability to inhibit anti-leishmanial macrophage activation, associated with the lower frequency of TNF-alpha(+) monocytes and ordinary levels of nitrite and nitrate are the major mechanisms associated with disease onset.

Adolescent↗
PubMed2005

[Significance of hepatitis B core antibody as the only marker of hepatitis B infection].

INTRODUCTION: Little is known about the clinical significance of the "anti-HBc alone" serological profile (absence of HBsAg and anti-HBs) in HBV infections. The objective of the present study was to estimate the prevalence of the anti-HBc alone immunological profile and the clinical-epidemiological characteristics of patients with this profile. METHODS: Prospective, cross-sectional, descriptive study performed in 2002 and including patients with anti-HBc alone (HBsAg-negative, anti-HBs-negative and anti-HBc-positive). All the cases identified underwent the following microbiological tests: IgM anti-HBc, HBeAg, anti-HBe, anti-HDV, anti-HCV, anti-HIV, as well as HBV-DNA testing by qualitative nested-PCR. Furthermore, studies of serum biochemical parameters, blood counts and coagulation, as well as a clinical-epidemiological interview were performed in all patients. RESULTS: Among 3900 patients studied, 195 (5%) presented the anti-HBc alone profile (48% were > 65 years old). Residual anti-HBs (< 10 mUI/mL) was found in 44% of cases and 33% were anti-HBe positive. HCV or HIV coinfection were seen in 38% and 8%, respectively. HBV-DNA was detected in 4.2% (5/120) of cases. Epidemiologically, detection of anti-HBc alone was casual in 60% of patients, whereas the remaining cases had a history of chronic liver disease (82% of these were anti-HCV positive). In a high percentage (63%) the transmission mechanism of HBV infection was unknown (11% intravenous drug abuser, 10% surgery, 6% transfusions). CONCLUSION: The anti-HBc alone pattern is a frequent finding, particularly in patients > 65 years old and in HCV or HIV coinfected patients. Although HBV-DNA was detected in a small percentage of cases, this test could be indicated in certain clinical situations (liver disease, coinfection, donors). Furthermore, this profile seems to be related with HCV infection; hence, we consider anti-HCV detection necessary in all patients with anti-HBc alone.

Adolescent↗
PubMed2006

The anti-IRBP IgG1 and IgG2a response does not correlate with susceptibility to experimental autoimmune uveitis.

Susceptibility to experimental autoimmune uveitis (EAU) in inbred mice has been associated with a dominant Th1 response. Elevated anti-inter-photoreceptor retinoid-binding protein (anti-IRBP) IgG2a/IgG1 antibody ratios have been implicated as candidate markers to predict disease severity. In the present study, both the anti-IRBP antibody isotype and severity of EAU phenotypes were examined in 4 non-isogenic genetically selected mouse lines to determine if they can be used as general markers of disease. Mice between 8 and 12 weeks old selected for high (H(III)) or low (L(III)) antibody response and for maximum (AIR(MAX)) or minimum (AIR(MIN)) acute inflammatory reaction (AIR) were immunized with IRBP. Each experiment was performed with at least 5 mice per group. EAU was evaluated by histopathology 21 days after immunization and the minimal criterion was inflammatory cell infiltration of the ciliary body, choroid and retina. Serum IgG1- and IgG2a-specific antibodies were determined by ELISA. EAU was graded by histological examination of the enucleated eyes. The incidence of EAU was lower in AIR(MIN) mice whereas in the other strains approximately 40% of the animals developed the disease. Low responder animals did not produce anti-IRBP IgG2a antibodies or interferon-gamma. No correlation was observed between susceptibility to EAU and anti-IRBP isotype profiles. Susceptibility to EAU is related to the intrinsic capacity to mount higher inflammatory reactions and increased production of anti-IRBP IgG2a isotype is not necessarily a marker of this immunologic profile.

Animals↗
PubMedDate not supplied

Immune profiles in hepatosplenic schistosomiasis mansoni after surgical treatments.

The hepatosplenic form of schistosomiasis mansoni sometimes induces bleeding in oesophageal varices that requires surgical treatment. Although splenectomy is often necessary these patients rarely present with septic events, a finding that may be related to changes in the immunological system. To investigate the immunological profiles of patients with schistosomiasis, we studied the B- and T-lymphocyte counts and the immunoglobulin A, G and M (IgA, IgG and IgM) levels in patients treated surgically and in those who were not operated on. Patients who underwent distal splenorenal shunt, preserving the spleen, showed significantly increased T-lymphocyte counts compared with healthy controls. The IgM and IgG levels were significantly increased compared with the healthy controls in patients submitted to partial and total splenectomy, respectively. The IgM level also tended to increase in patients who were not operated on compared with the controls. These results suggest that chronic schistosomiasis may influence the immune system.

Adolescent↗
PubMedDate not supplied

Systemic production of IL-12 by naked DNA mediated gene transfer: toxicity and attenuation of transgene expression in vivo.

BACKGROUND: IL-12 is a potent antitumor cytokine for cancer gene therapy. Previously, we demonstrated that single systemic administration of naked DNA (encoding IL-12) could serve as a good model for in vivo evaluation of the antitumor effect of a candidate gene (unpublished data). In the present study, we propose that this gene delivery method could be a very useful model for in vivo evaluation of the toxicity of a given therapeutic gene (using IL-12 as an example). By comparing the toxicities and the effects of initial IL-12 administration on subsequent transgene expression, both IL-12 gene delivery and recombinant murine IL-12 protein (rmIL-12) administration showed similar toxicity profiles. METHODS: Naked DNA encoding murine IL-12 (mIL-12) was delivered into mice by systemic administration. Toxicity profiles of mice treated with DNA or rmIL-12 were compared. RESULTS: Systemic administration of naked DNA encoding mIL-12 resulted in very similar toxicity as rmIL-12 with respect to liver enzyme, hematological and immunological profiles. Repeated injection of mIL-12 gene did not recover a high level of mIL-12 production as the first injection. Moreover, initial mIL-12 administration resulted in inhibition of subsequent reporter gene expression with both viral and non-viral promoters (CMV, human alpha-antitrypsin or chicken beta-actin promoter). This transgene inhibition effect was entirely mediated by IFN-gamma as the transgene expression was fully recovered in IFN-gamma knockout mice. CONCLUSIONS: Systemic IL-12 therapy, with either a protein or gene therapy approach, resulted in comparable liver and systemic toxicities. Refractoriness of mIL-12 production by subsequent administration of mIL-12 gene was observed. The transgene attenuation effect of IL-12 pre-dosing (either by IL-12 or rmIL-12), mediated by IFN-gamma, provided important insights for the design of IL-12 combination gene therapy and the improvement of gene vectors for IL-12 therapy. The present results show that simple injection of naked DNA could serve as a good model for in vivo evaluation of the toxicity of a candidate therapeutic gene.

Animals↗
PubMed2005

Rheumatologic manifestations in patients with selected primary immunodeficiencies evaluated at the University Hospital.

OBJECTIVE: To characterize an IgA deficient and common variable immunodeficiency (CVI) group of patients in terms of the presence of rheumatologic manifestations. BACKGROUND: Although the molecular basis of some of the primary immunodeficiencies has been elucidated, it has not been possible to explain why in most cases these conditions are often associated with autoimmune manifestations, besides infections. The concomitant inability to fight infections adequately (immunodeficiency) and an inordinate reaction of the immune system to self components (autoimmunity) has been a perplexing situation. METHODS: The clinical and immunological profile of 71 patients fulfilling the diagnostic criteria of selective IgA deficiency (n=38) and common variable immunodeficiency (n=33) were evaluated for concurrent rheumatologic manifestations after a thorough medical history, physical examination and pertinent immunological parameters. RESULTS: The most common autoimmune conditions identified in patients with selective IgA deficiency were Crohn's disease and systemic lupus erythematosus (SLE); while immune thrombocytopenic purpura and Crohn's disease were the most common disorders associated to CVI. Anti-IgA antibodies were only found in 26.6% (95% C.I. 10.1-51.4) of patients with selective IgA deficiency but were present in all patients with that condition and SLE. Fifty per cent patients with CVI and ITP exhibited ANA positivity. CONCLUSIONS: The IgA-deficient group of patients in this study showed a higher prevalence of autoimmune conditions and greater positivity for ANA as compared to patients with CVI. In contrast to other reports with around 44% positivity of anti-IgA antibodies in selective IgA patients these were only present in 263% of patients with that disorder in this study. The high prevalence of antinuclear antibodies not associated with any clinical autoimmune condition in the IgA-deficient patients in this study will need to be further explored to ascertain why IgA-deficient patients may be at an increased risk of autoimmunity. Inflammatory bowel disease (Crohn's disease and ulcerative colitis) constituted the most common clinical autoimmune manifestations in both groups of patients studied. ITP was the commonest organ-specific autoimmune condition identified in the CVI group, as reported in previous publications. The limited number of patients studied does not allow a reliable estimate of the prevalence of SLE in the IgA-deficient population analyzed. The observed differences in frequency of positive antibodies and clinical autoimmune conditions in our patients cannot be taken as typical due to the limited number examined and the exclusion of pediatric cases in the IgA deficient group. A continued surveillance of these patients might help to establish more definite tendencies regarding rheumatologic manifestations in primary immunodeficiencies.

Adolescent↗
PubMed1993

A case-control and family study of Waldenstrom's macroglobulinemia.

Waldenstrom's macroglobulinemia (WM) is a rare disorder of lymphoid and plasma cells characterized by an immunoglobulin M (IgM) monoclonal gammopathy, clinical and immunopathologic similarities with other lymphoproliferative neoplasms, but the etiology of which is unknown. We undertook the first case-control study of this disorder among 65 cases, comprising 87% of all WM patients diagnosed during 1969-1983 in the greater Baltimore, Maryland area. Compared with 213 hospital controls without cancer, cases were slightly better educated, but there were otherwise no differences in sociodemographic factors, history of prior medical conditions, medication use, cigarette smoking, alcohol consumption, specific occupational exposures, employment in any particular industries or occupations, or familial cancer history. Cases were more likely than controls to have first-degree relatives with a history of pneumonia, diphtheria, rheumatic fever, and diabetes mellitus. An exploratory evaluation of immunologic profiles of first-degree relatives of 48% of families of cases revealed that relatives of two cases had asymptomatic IgM (> 750 mg/dl) monoclonal gammopathy and close to 40% of the 109 evaluated had diverse immunologic abnormalities. Larger population-based case-control studies are needed to further evaluate the suggestive evidence of immune dysfunction among families of WM cases.

Aged↗
PubMed2005

B1 lymphocytes and myeloid dendritic cells in lymphoid organs are preferential extratumoral sites of parvovirus minute virus of mice prototype strain expression.

Due to their oncolytic properties and apathogenicity, autonomous parvoviruses have attracted significant interest as possible anticancer agents. Recent preclinical studies provided evidence of the therapeutic potential of minute virus of mice prototype strain (MVMp) and its recombinant derivatives. In a murine model of hemangiosarcoma, positive therapeutic outcome correlated with high intratumoral expression of MVMp-encoded genes in tumors and lymphoid organs, especially in tumor-draining lymph nodes. The source and relevance of this extratumoral expression, which came as a surprise because of the known fibrotropism of MVMp, remained unclear. In the present study, we investigated (i) whether the observed expression pattern occurs in different tumor models, (ii) which cell population is targeted by the virus, and (iii) the immunological consequences of this infection. Significant MVMp gene expression was detected in lymphoid tissues from infected tumor-free as well as melanoma-, lymphoma-, and hemangiosarcoma-bearing mice. This expression was especially marked in lymph nodes draining virus-injected tumors. Fluorescent in situ hybridization analysis, multicolor fluorescence-activated cell sorting, and quantitative reverse transcription-PCR revealed that MVMp was expressed in rare subpopulations of CD11b (Mac1)-positive cells displaying CD11c+ (myeloid dendritic cells [MDC]) or CD45B (B220+ [B1 lymphocytes]) markers. Apart from the late deletion of cytotoxic memory cells (CD8+ CD44+ CD62L-), this infection did not lead to significant alteration of the immunological profile of cells populating lymphoid organs. However, subtle changes were detected in the production of specific proinflammatory cytokines in lymph nodes from virus-treated animals. Considering the role of B1 lymphocytes and MDC in cancer and immunological surveillance, the specific ability of these cell types to sustain parvovirus-driven gene expression may be exploited in gene therapy protocols.

Animals↗