Type-Specific Streptococcal Antibodies in Pyodermal Nephritis (original) (raw)
emm Typing and Validation of Provisional M Types for Group A Streptococci
Emerging Infectious Diseases, 1999
The Lancefield M-typing system, a typical serologic system based on antigen-antibody reactions, is dependent on the preparation of type-specific antisera and extraction of a protein identified as M protein on the surface of group A streptococci (GAS) (1). The antisera against the M-protein antigens are produced with whole-cell streptococcal vaccines used to immunize rabbits. Acceptable antisera contain specific-precipitin antibodies and type-specific antibodies that must enhance the phagocytosis of the strain used to immunize the rabbit (2,3). The precipitin antibodies are made specific by absorption of the serum with streptococcal cells to remove the carbohydrate group antibodies and any crossreactive precipitin antibody to heterologous M-type strains. Each rabbit antiserum is tested for reaction with antigens of all known M types. Approximately half of GAS strains produce an apoproteinase, an enzyme that causes mammalian serum to increase in opacity. This reaction is called the serum opacity factor reaction, and the responsible enzyme is referred to as opacity factor (OF). The OF enzymes are OF type-specific because each M type that produces OF can induce type-specific OF antibodies that can be used in OF inhibition tests (3,4). Preparation of the OF antisera and specific details of the OF tests are described elsewhere (3,4). Some laboratories have used OF typing to predict M types in epidemiologic investigations. Even though it is not uniformly agreed that OF typing antisera results should be reported as M or provisional M-typing results, anti-OF antisera in many situations predict the M type in a typespecific manner. For reporting purposes, if
Changing types of nephritogenic streptococci in Trinidad
Journal of Clinical Investigation, 1971
A B STRA CT The relation of seven different M types of streptococci to acute glomerulonephritis associated with skin lesions in South Trinidad has been studied by means of type-specific antibody assays as well as by iso- lation and identification of the strains. The data indicate that, one after another, five of these strains have prevailed among patients with acute glomerulonephritis dur- ing the past five years. At least three of the strains (M-types 55, 49, 57, and/or 60) were associated with epidemic increases in nephritis cases. The appearance of five consecutively predominant types of nephritogenic streptococci during a relatively short period of time is in contrast to the continuing prevalence of M-type 12 strains among nephritogenic streptococci primarily as- sociated with respiratory infections in temperate zones. These observations suggest that the skin sores com- monly found on children in tropical Trinidad, provide a particularly suitable environment for development of nephritogenic types. It remains to be seen whether these types will recur or whether new types will continue to emerge in Trinidad.
Kidney International, 2005
Is the nephritogenic antigen in post-streptococcal glomerulonephritis pyrogenic exotoxin B (SPE B) or GAPDH? Background. Acute glomerulonephritis can follow infection by group A streptococci. An immune-complex pathogenesis is accepted, but the causative antigen(s) is still controversial. In recent years, 2 streptococcal antigens, the cationic cysteine proteinase exotoxin B (SPE B) and the plasmin receptor, a glyceraldehyde phosphate dehydrogenase (Plr, GAPDH) have attracted attention because: (1) they were localized in glomeruli in patients with acute post-streptococcal glomerulonephritis (APSGN); and (2) serum antibody to these antigens was associated with nephritogenic streptococcal infections. To date, putative nephritogens were always tested independently. Here, the relevance of SPE B and GAPDH was evaluated in the same renal biopsies and serum samples of welldefined APSGN patients. Methods. Renal biopsies (17 patients) and serum samples (53 patients) with APSGN and appropriate controls were examined. Immunofluorescent staining of frozen sections was performed using specific antibodies to SPE B and GAPDH. Serum antibodies were investigated by both enzyme-linked immunosorbent assay (ELISA) and Western blot methodology. Results. Glomerular deposits of SPE B were demonstrated in 12/17 APSGN biopsies, and 2 cases were borderline; circulating antibodies were found in all instances (53/53 patients). Glomerular deposition of GAPDH was detected in 1/17 biopsies, and 2 cases were borderline; circulating antibodies were found in 5/47 patients. In 31 control biopsies, only weak staining for each antigen was found in 2 cases. Conclusion. In this study, glomerular deposits of and antibody response to zymogen/SPE B are more consistently present in APSGN than deposits and antibody response to GAPDH. Zymogen/SPE B is likely to be the major antigen involved in the pathogenesis of most cases of APSGN.
Group A streptococcal antigen in the glomeruli of children with henoch-schönlein nephritis
American Journal of Kidney Diseases, 2003
Background: Although the pathogenesis of Henoch-Schö nlein nephritis (HSN) remains unclear, there is substantial evidence that it is an immune complex-mediated disease. HSN is preceded by upper-respiratory tract infection in 30% to 50% of patients, but there is no evidence that group A streptococcal (GAS) infection has a pathogenetic role in this disease. Recently, nephritis-associated plasmin receptor (NAPlr), a GAS antigen, was found primarily in the glomerular mesangium of patients with early-stage acute poststreptococcal glomerulonephritis. Methods: To determine the possible role of NAPlr in HSN, expression of the receptor was determined in glomeruli using fluorescein isothiocyanate-labeled rabbit polyclonal anti-NAPIr antibody, and serum antistreptolysin O (ASO) titers were measured in children with HSN. Results: Ten of 33 patients (30%) with HSN showed segmental or global mesangial staining with NAPlr antibody, whereas only 4 of 120 patients (3%) with other renal diseases were positive (P < 0.001, Fisher's exact test). Patients with HSN also showed significantly greater ASO titers than patients with other renal diseases (P ؍ 0.03, Mann-Whitney U test). Serum ASO titers were significantly greater in patients with HSN with than without glomerular NAPlr antigen (P ؍ 0.03, Mann-Whitney U test). Conclusion: These findings suggest that the deposition of NAPlr in the mesangium, induced by GAS infection, may have a role in the pathogenesis of HSN in some patients.
Upsala Journal of Medical Sciences, 2005
We studied history, renal histopathology and microbiology of an epidemic of acute glomerulonephritis associated with throat infections and uncommon culture results in four neighbour families. A 40-year-old man (index patient) was referred to a university hospital for dialysis and kidney biopsy due to a suspected acute glomerulonephritis. An acute tonsillitis had preceded the condition. Penicillin treatment had been started four days before the discovery of renal failure. Throat swabs were positive for-hemolytic streptococci, group C (GCS). GCS were also found in throat cultures from his wife and two of their children. The bacteria were typed as Streptococcus constellatus. A third child had S. constellatus expressing Lancefield antigen group G. A neighbour and two of his children fell ill the following week with renal involvement. Throat swabs from both these children were positive for S. constellatus. His third child had erythema multiforme and S. constellatus in the throat while a fourth child hadhemolytic streptococci group A; Streptococcus pyogenes. Kidney biopsies on the index patient and his neighbour showed an acute diffuse prolipherative glomerulonephritis compatible with acute post-streptococcal nephritis and microbiological analysis of renal tissue revealed in both cases S. pyogenes and S. constellatus. The
Post-streptococcal acute glomerulonephritis in Chile—20 years of experience
Pediatric Nephrology, 2004
In order to characterize the epidemiological and clinical picture of post-streptococcal acute glomerulonephritis (PSAGN), a prospective study was designed to investigate all admissions to a general hospital of a local health service in Chile. The protocol included the investigation of previous streptococcal infections (SI), clinical symptoms and signs, socioeconomic situation (SES), throat and skin swabs for the isolation of group A beta-hemolytic streptococci, sequential determination of serum antistreptolysin O (ASO) titer, anti-DNAase B antibodies, and C3. During the 20 years studied, 926 cases were admitted (56% males). Incidence showed an endemic period (EP) 1980–1983, an epidemic outbreak (EO) 1984–1989, and a late period (LP) 1990–1999, with a rate per 100,000 inhabitants of 6.2, 13.2, and 1.7, respectively. The clinical picture was similar in the three periods. SES was homogeneous, with 80% of the population in low and middle-low categories. The average size of the family was 6.9 compared with 4.8 in the general population. Pyoderma was more frequent than pharyngeal infection, and more so during the EO. The isolation rate of group A beta-hemolytic streptococci from the pharynx was 20% compared with 60% from skin swabs. During EP, the most prevalent serotypes were T14-M0 and T1-M1 from the pharynx and TImp19-M0 from the skin. During EO, T14-M0 was more prevalent (30%). M or T classification was possible in EP and EO in 80%–85% of all strains isolated from the two locations. Significant titers for ASO and anti-DNAase B were found on admission: 55% and 75%, respectively. Both tests allowed identification of 100% of previous SI. In conclusion, the incidence of PSAGN had an uneven trend during the observed period. EO was mainly due to skin infection and a predominance of one serotype, T14-MO, was observed. After the EO, the yearly rate gradually decreased from 13.2 in 1988 to 0.0 in 1999, a rate similar to that of industrialized nations.
Rapid Multiplex Assay for Serotyping Pneumococci with Monoclonal and Polyclonal Antibodies
Journal of Clinical Microbiology, 2005
We have developed and characterized a rapid semiautomated pneumococcal serotyping system incorporating a pneumococcal lysate preparation protocol and a multiplex serotyping assay. The lysate preparation incorporates a bile solubility test to confirm pneumococcal identification that also enhances assay specificity. The multiplex serotyping assay consists of 24 assays specific for 36 serotypes: serotypes 1, 2, 3, 4, 5, 6A, 6B, 7A/7F, 8, 9L/9N, 9V, 10A/10B/39/(33C), 11A/11D/11F, 12A/12B/12F, 14, 15B/(15C), 17F, 18C, 19A, 19F, 20, 22A/22F, 23F, and 33A/33F. The multiplex assay requires a flow cytometer, two sets of latex particles coated with pneumococcal polysaccharides, and serotype-specific antibodies. Fourteen newly developed monoclonal antibodies specific for common serotypes and a pool of polyclonal rabbit sera for some of the less-common serotypes are used. The two monoclonal antibodies specific for serotypes 18C and 23F recognize serotypespecific epitopes that have not been previously described. These monoclonal antibodies make the identification of the 14 common serotypes invariant. The specificity of the serotyping assay is fully characterized with pneumococci of all known (i.e., 90) serotypes. The assay is sensitive enough to use bacterial lysates diluted 20 fold. Our serotyping system can identify not only all the serotypes in pneumococcal vaccines but also most (>90%) of clinical isolates. This system should be very useful in serotyping clinical isolates for evaluating pneumococcal vaccine efficacy.
Acute Post-Streptococcal Glomerulonephritis in a Known Nephrotic Syndrome Patient: A Case Report
GEGET
Nephrotic syndrome (NS) is one of the most common childhood kidney diseases. Idiopathic NS (INS) can affect children of any age from infancy to adolescence and predominantly occurs in those aged 1-6 years. Acute glomerulonephritis (AGN) is a disease characterized by edema, oliguria, hematuria, and hypertension. It characterized by inflammation of the glomerulus with proliferation of cellular elements secondary to an immunologic mechanism. Acute poststreptococcal glomerulonephritis (APSGN) results from an antecedent infection of the skin (impetigo) or throat (pharyngitis) caused by nephritogenic strains of group A betahemolytic streptococci. Here we present a case of APSGN in a patient with known steroid dependent INS.
Journal of Nephropathology, 2016
Background: Anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN) can be classified into; focal, crescentic, mixed and sclerotic classes. Macrophages and T lymphocytes are key players in mediating renal injury. The frequency of macrophage and T lymphocytes in different histological classes is unclear. Objectives: We examined the frequency of macrophage and T lymphocyte markers in AAGN and assessed their correlation with renal function at presentation. Patients and Methods: Renal biopsies from 38 patients were included in immunohistochemistry analysis of macrophages (CD68, sialoadhesin [Sn] and mannose receptor [MR]) and T cells (CD4 and CD8) markers. The frequency of these markers in glomerular, periglomerular and interstitial compartments were measured in a blinded fashion. Biopsies were allocated a histological class of focal, crescentic, mixed or sclerotic. Scores were then matched to histological class and assessed for correlation with renal function. Results: The biopsies were crescentic 19 (50%), focal 10 (26.3%), mixed 6 (15.7%) and sclerotic 3 (8%). Interstitial CD68+ macrophages and CD8+ T lymphocytes showed best correlation with renal function at the time of presentation. CD68+ macrophages were significantly increased in crescentic compared to focal AAGN. MR+ macrophages, CD4 and CD8 T cells were also elevated in the interstitium of crescentic compared to focal group. Conclusions: In this study interstitial CD68 and CD8 showed the highest association with the renal function at presentation. Differences in the cellular infiltrate between focal and crescentic AAGN were related to CD68+ macrophages and to interstitial MR+ macrophages and T lymphocytes. Further studies are needed to assess these differences across all four histological categories.
Local antibody production in experimental pyelonephritis: amount, avidity, and immunoglobulin class
Infection and Immunity
Local antibody formation in infected rabbit kidneys was studied with three techniques: the ammonium sulfate precipitation technique, the enzyme-linked immunosorbent assay, and by binding of newly synthesized "4C-labeled antibodies to heat-killed bacteria. Local antibody was detected by day 11 of infection with all three techniques, and a significant correlation was found in titers by all three methods. In these studies, antibody synthesized early was in IgG and IgA class, whereas IgM antibodies appeared later (day 20) in the antibody response. No maturation of avidity of local antibody was noted with time. Since it was necessary to use different animals at each test occasion, individual differences in avidity could account for failure to note an increase in avidity with time.
Pediatric Rheumatology, 2019
Background: Nephritis is the most important chronic complication of IgA Vasculitis (IgAV)/Henoch-Schönlein purpura (IGAV/HSP) and thus the main prognostic factor of this most common childhood vasculitis. Since the prognosis and treatment selection depends on the mode of interpretation of biopsy material, in this manuscript we have presented several issues related to the uneven application of different histological classifications in IgAV/Henoch-Schönlein purpura nephritis (HSPN). The nephritis of IgAV/IGAV/HSP will be abbreviated as HSPN for this paper. Main body: In clinical practice we use different histological classifications for HSPN. It is not known which of these classifications best correlates with severity of renal disease and renal outcome in IgAV/IGAV/HSP. One of the major problem with existing histological classifications is that there is no consensus on the implementation of biopsy in the treatment of HSPN. There is a histologic classification system conventionally used in HSPN, of the International Study of Kidney Disease in Children (ISKDC). On the other hand there is the new classification system suggested for IgA nephropathy, the Oxford classification. The latter has been validated only in IgA nephropathy. There are also two further histologic classifications of Haas and Koskela that have been developed. Current treatment strategies in HSPN are not standardised nor predominantly based on histological classification. Conclusion: One of the possible solutions to problems related to the application of different histological classification in HSPN is the implementation of multicenter multinational prospective studies with joint collaboration between pediatric rheumatologists, nephrologists and nephropathologists to correlate the clinical features and outcome with the classification systems as well among the classifications. This classification should be the basis for the construction of guidelines for the treatment of patients with HSPN.
Acute Pyelonephritis in Adults
Archives of internal medicine, 2003
Background: To formulate a classification tool for early recognition of patients admitted with acute pyelonephritis (AP) who are at high risk for failure of treatment or for death. Methods: A retrospective chart review of 225 patients (102 men) admitted with AP. We considered 13 potential risk factors in a multivariate analysis. Results: Recent hospitalization, previous use of antibiotics, and immunosuppression were found to be independent correlates of the prevalence of resistant pathogens in both sexes. Additional predictors included nephrolithiasis in women and a history of recurrent AP in men. Prolonged hospitalization should be expected for a man with diabetes and long-term catheterization who is older than 65 years or for a woman of any age with the same characteristics, when the initial treatment was changed according to the results of urine culture. For mortality prediction, we derived an integer-based scoring system with 6 points for shock, 4 for bedridden status, 4 for age greater than 65 years, and 3 for previous antibiotic treatment for men and 6 points for shock, 4 for bedridden status, 4 for age greater than 65 years, and 3 for immunosuppression for women. Among patients with at least 11 points, the risk for in-hospital death was 100% for men and 91% for women. Conclusions: Simple variables available at presentation can be used for risk stratification of patients with AP. The additional identification of certain risk factors by means of a carefully obtained history could contribute to early recognition of patients infected by resistant bacteria and optimize the selection of antimicrobial agents.
Atypical Clinical Manifestations of Acute Poststreptococcal Glomerulonephritis
2011
Acute poststreptococcal glomerulonephritis (APSGN) is one of the most common and important renal diseases resulting from a prior infection with group A β-hemolytic streptococcus (GAS) (Ash and Ingulli, 2008). Typical clinical features of the disease include an acute onset with gross hematuria, edema, hypertension and moderate proteinuria (acute nephritic syndrome) 1 to 2 weeks after an antecedent streptococcal pharyngitis or 3 to 6 weeks after a streptococcal pyoderma Rodriguez-Iturbe & Mezzano, 2009). Gross hematuria usually disappears after a few days, while edema and hypertension subside in 5 to 10 days (Rodriguez-Iturbe & Mezzano, 2009). Although the incidence of APSGN appears to be decreasing in industrialized countries, more than 472,000 cases with APSGN are estimated to occur each year worldwide, with 97% of them occurring in developing countries (Carapetis et al., 2005; Eison et al., 2010). APSGN occurs most commonly in children, 5 to 12 years old , although 5 to 10 percent of the patients are more than 40 years old . The immediate and long-term prognoses of APSGN are excellent for children, assuming it is diagnosed in a timely fashion . In contrast, adult patients with APSGN show markedly worse prognoses both in the acute phase and in the long-term . The most popular theory of the pathogenic mechanism of APSGN has been the immunecomplex theory, which involves the glomerular deposition of nephritogenic streptococcal antigen and subsequent formation of immune complexes in situ and/or the deposition of circulating antigen-antibody complexes . Two antigens have been actively investigated as the potential causes of APSGN (Rodriguez-Iturbe & Musser, 2008): the nephritis-associated plasmin receptor (NAPlr) also known as streptococcal glyceraldehyde-3-phosphate dehydrogenase , and a cationic cysteine proteinase known as streptococcal pyogenic exotoxin B (SPEB) . Patients with APSGN sometimes exhibit atypical or unusual clinical manifestations, which may lead to diagnostic delay or misdiagnosis of the disorder . Recognition of these unusual manifestations in cases of APSGN is important in order to assure that the patient receives adequate treatment. In this chapter, I review the atypical clinical manifestations of APSGN. An Update on Glomerulopathies -Clinical and Treatment Aspects 152 Atypical manifestations of APSGN can be classified as the following: co-occurrence of immune-mediated diseases; non immune-mediated complications; and unusual clinical presentations or courses (Table ). Immune-mediated diseases Acute rheumatic fever (ARF) Poststreptococcal reactive arthritis (PSRA) Vasculitis Immune thrombocytopenic purpura (ITP) Autoimmune hemolytic anemia (AIHA) Diffuse alveolar hemorrhage (DAH) Uveitis Non immune-mediated complications Posterior reversible encephalopathy syndrome (PRES) Thrombotic microangiopathy (TMA) Gallbladder wall thickening Unusual clinical presentations or courses Minimal urinary abnormalities Recurrence Table 1. Atypical manifestations of acute poststreptococcal glomerulonephritis Immune-mediated diseases most likely result from immune-complex formation between streptococcal antigens and their associated antibodies, and include acute rheumatic fever, poststreptococcal reactive arthritis, vasculitis, immune thrombocytopenic purpura, autoimmune hemolytic anemia, diffuse alveolar hemorrhage and uveitis. Acute rheumatic fever (ARF) is an autoimmune disease that follows infection by GAS and is characterized by inflammation of several tissues that gives rise to typical clinical characteristics (the so-called Jones criteria) including carditis/valvulitis, arthritis, chorea, erythema marginatum, and subcutaneous nodules . ARF is rare in developed countries, but it remains common in developing countries and some poor, mainly indigenous populations of wealthy countries Carapetis et al., 2005). Although both ARF and APSGN develop following GAS infection, the two diseases have different epidemiology, immunology and bacteriology, and simultaneous occurrence of them in the same patient is rare (Lin et al., 2007). Since Gibney et al. first reported a patient with co-occurrence of ARF and histologically proven APSGN (Gibney et al., 1981), seventeen patients with concurrent ARF and APSGN have been reported (
Kidney International, 1998
Immunohistochemical and serological evidence for the role of streptococcal proteinase in acute post-streptococcal glomerulonephritis. Background. We have previously demonstrated the preferential secretion of streptococcal proteinase or streptococcal pyrogenic exotoxin B (SPEB) by nephritic strains of Group A streptococci isolated from the skin or throat of patients with acute poststreptococcal glomerulonephritis (APSGN). Methods. To further explore the possible role of SPEB in APSGN, we performed ELISA studies to detect anti-SPEB antibodies in the sera of patients with APSGN, acute rheumatic fever (ARF), scarlet fever (SF) and normal children. Using ELISA, anti-SPEB titers on acute and convalescent APSGN sera were measured to determine immunity to APSGN. We also performed immunofluorescence studies on APSGN and non-APSGN kidney biopsies to probe for the presence and localization of SPEB. Results. Our data show that anti-SPEB antibodies are present in APSGN sera and antibody titers are significantly higher than in ARF, SF and normal sera. Anti-SPEB titers tend to rise acutely and decrease with time but do not reach baseline after one year. When kidney biopsies were probed with rabbit anti-SPEB antibody, 12 of 18 (67%) of the APSGN cases were positive while only 4 of 25 (16%) of the non-APSGN cases were positive. Conclusions. In summary, we were able to demonstrate unique reactivity to SPEB in human sera and kidney biopsies of APSGN suggesting a significant role of this toxin in the pathogenesis of acute post-streptococcal glomerulonephritis.