Pathologic differentiation between lupus and nonlupus membranous glomerulopathy

Pathologic differentiation between lupus and nonlupus membranous glomerulopathy. The following clinical and pathologic features were evaluated in 170 patients with electron microscopically documented membranous glomerulopathy: age, sex, race, American Rheumatism Association lupus criteria, serum ANA, serum complement, glomerular hypercellularity, stage of subepithelial dense deposits, endothelial tubuloreticular inclusions, tubular basement membrane deposits, tissue ANA, glomerular deposition of IgG, IgM, IgA, C3, C4, and C1q. At the time of biopsy 148 patients had no clinical evidence for lupus, and 22 had a clinical diagnosis of lupus. Six additional patients eventually developed overt lupus after an average of 12 months. Incidences of serologic and pathologic features in lupus as compared with nonlupus membranous glomerulopathy were determined. These data were used to calculate sensitivity, specificity, positive and negative predictive values, and overall efficiency of each parameter in differentiating between lupus and nonlupus membranous glomerulopathy. In general, serologic, morphologic and immunohistopathologic features are more accurate at ruling out lupus than making the diagnosis of lupus. However, a number of features are significantly more frequent in lupus membranous glomerulopathy. Therefore, identification of these features, especially more than one, warrants a high suspicion of lupus rather than nonlupus membranous glomerulopathy even in patients without clinically overt systemic lupus erythematosus. The positive/negative predictive values of some of the pathologic features studied are as follows: mesangial dense deposits 63/99, subendothelial dense deposits 77/93, tubuloreticular inclusions 61/96, intense C1q deposition 47/95, tubular basement membrane deposits 100/87, and glomerular hypercellularity 26/86.Différentiation pathologique entre glomérulopathie extra-membraneuse lupique et non lupique. Les caractéristiques cliniques et pathologiques suivantes ont été évaluées chez 170 malades atteints de glomérulopathie extra-membraneuse documentée par microscopie électronique: l'âge, le sexe, la race, les critères de lupus de l'American Rheumatism Association, les ANA sériques, le complément sérique, l'hypercellularité glomérulaire, le stade des dépôts denses sous-épithéliaux, les inclusions endothéliales tubuloréticulaires, les dépôts dans la membrane basale tubulaire, les ANA tissulaires, les dépôts glomérulaires d'IgG, IgM, IgA, C3, C4, et C1q. Au moment de la biopsie, 148 malades n'avaient pas d'argument clinique pour un lupus, et 22 avaient un diagnostic clinique de lupus. Six malades supplémentaires ont développé un lupus patent après une moyenne de 12 mois. L'incidence des caractéristiques sérologiques et pathologiques dans la glomérulopathie extra-membraneuse lupique ou non lupique a été déterminée. Ces données ont été utilisées pour calculer la sensibilité, la spécificité, les valeurs prédictives positives et négatives, et l'efficacité globale de chaque paramètre pour différencier entre glomérulopathie extra-membraneuse lupique ou non lupique. D'une façon générale, les caractéristiques sérologiques, morphologiques et immunohistopathologiques sont plus puissantes pour éliminer le lupus que pour faire le diagnostic de lupus. Cependant, un certain nombre de caractéristiques sont significativement plus fréquentes dans la glomérulopathie extra-membraneuse lupique. C'est pourquoi la mise en évidence de ces caractéristiques, surtout s'il y en a plus d'une, apporte une forte suspicion de glomérulopathie extra-membraneuse plus lupique que non lupique, même chez des malades sans lupus erythémateux disséminé cliniquement patent. Les valeurs prédictives positives/négatives de certaines des caractéristiques pathologiques étudiées sont les suivantes: dépôts denses mésangiaux 63/99, dépôts denses sous-endothéliaux 77/93, inclusions tubuloréticulaires 61/96, dépôts intenses de C1q 47/95, dépôts dans la membrane basale tubulaire 100/87, et hypercellularité glomérulaire 26/86

CD14 mediates the innate immune responses to arthritopathogenic peptidoglycan–polysaccharide complexes of Gram-positive bacterial cell walls

Bacterial infections play an important role in the multifactorial etiology of rheumatoid arthritis. The arthropathic properties of Gram-positive bacteria have been associated with peptidoglycan–polysaccharide complexes (PG-PS), which are major structural components of bacterial cell walls. There is little agreement as to the identity of cellular receptors that mediate innate immune responses to PG-PS. A glycosylphosphatidylinositol-linked cell surface protein, CD14, the lipopolysaccharide receptor, has been proposed as a PG-PS receptor, but contradictory data have been reported. Here, we examined the inflammatory and pathogenic responses to PG-PS in CD14 knockout mice in order to examine the role for CD14 in PG-PS-induced signaling. We found that PG-PS-induced responses in vitro, including transient increase in intracellular calcium, activation of nuclear factor-κB, and secretion of the cytokines tumor necrosis factor-α and interleukin-6, were all strongly inhibited in CD14 knockout macrophages. In vivo, the incidence and severity of PG-PS induced acute polyarthritis were significantly reduced in CD14 knockout mice as compared with their wild-type counterparts. Consistent with these findings, CD14 knockout mice had significantly inhibited inflammatory cell infiltration and synovial hyperplasia, and reduced expression of inflammatory cytokines in PG-PS arthritic joints. These results support an essential role for CD14 in the innate immune responses to PG-PS and indicate an important role for CD14 in PG-PS induced arthropathy

Mast cell activation by group A streptococcal polysaccharide in the rat and its role in experimental arthritis.

Acute edematous responses were induced in Sprague-Dawley rats by the intravenous injection of group-specific polysaccharide (PS) isolated from group A streptococci. Thirty minutes after the intravenous injection of PS there was marked degranulation of subcutaneous and periarticular mast cells in all 4 feet, carbon particle labeling of adjacent venules, and an 8-fold increase in Evans blue dye content of the extremities. This acute reaction to PS was completely blocked by pretreatment with compound 48/80, but the polyarticular relapsing arthritis following the systemic injection of an arthropathic dose of streptococcal cell wall fragments containing large, covalently bound peptidoglycan-polysaccharide (PG-PS) was not blocked

Associations between Burkitt Lymphoma among Children in Malawi and Infection with HIV, EBV and Malaria: Results from a Case-Control Study

Background: Burkitt lymphoma, a childhood cancer common in parts of sub-Saharan Africa, has been associated with Epstein Barr Virus (EBV) and malaria, but its association with human immunodeficiency virus (HIV) is not clear.Methodology/Principal Findings: We conducted a case-control study of Burkitt lymphoma among children (aged <= 15 years) admitted to the pediatric oncology unit in Blantyre, Malawi between July 2005 and July 2006. Cases were 148 children diagnosed with Burkitt lymphoma and controls were 104 children admitted with non-malignant conditions or cancers other than hematological malignancies and Kaposi sarcoma. Interviews were conducted and serological samples tested for antibodies against HIV, EBV and malaria. Odds ratios for Burkitt lymphoma were estimated using unconditional logistic regression adjusting for sex, age, and residential district. Cases had a mean age of 7.1 years and 60% were male. Cases were more likely than controls to be HIV positive (Odds ratio (OR)) = 12.4, 95% Confidence Interval (CI) 1.3 to 116.2, p = 0.03). ORs for Burkitt lymphoma increased with increasing antibody titers against EBV (p = 0.001) and malaria (p = 0.01). Among HIV negative participants, cases were thirteen times more likely than controls to have raised levels of both EBV and malaria antibodies (OR = 13.2; 95% CI 3.8 to 46.6; p = 0.001). Reported use of mosquito nets was associated with a lower risk of Burkitt lymphoma (OR = 0.2, 95% CI, 0.03 to 0.9, p = 0.04).Conclusions: Our findings support prior evidence that EBV and malaria act jointly in the pathogenesis of Burkitt lymphoma, suggesting that malaria prevention may decrease the risk of Burkitt lymphoma. HIV may also play a role in the etiology of this childhood tumor

Cationic polyelectrolytes: A new look at their possible roles as opsonins, as stimulators of respiratory burst in leukocytes, in bacteriolysis, and as modulators of immune-complex diseases (A review hypothesis)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44497/1/10753_2004_Article_BF00915991.pd