Immune response of tonsillar lymphocytes to Haemophilus parainfluenzae in patients with IgA nephropathy

The pathogenesis of IgA nephropathy (IgAN) is unclear. We have previously shown glomerular deposition of Haemophilus parainfluenzae (HPI) antigens and the presence of IgA antibody against HPI antigens in patients with IgAN. We examined the immune response to HPI antigens in tonsillar lymphocytes from patients with IgAN. Lymphocytes isolated from the palatine tonsils of 13 IgAN patients and 16 patients with chronic tonsillitis but without renal disease were used as controls. We examined lymphocyte proliferation and production of IgA antibody against HPI antigens by measuring thymidine uptake and IgA antibody in culture supernatants after lymphocyte incubation with HPI antigens. Patients with IgAN showed a significantly higher stimulation index to HPI antigens (thymidine incorporation in tonsillar lymphocytes with HPI/thymidine incorporation in unstimulated tonsillar lymphocytes) than controls (P < 0.002). Lymphocytes from patients with IgAN also showed a significantly higher level of IgA antibody and IgA1 antibody against HPI antigens in culture supernatants than lymphocytes from controls (P = 0.0002 and P = 0.004, respectively). Our results suggest that HPI antigens stimulate tonsillar T and B lymphocytes in patients with IgAN and that an immune response to HPI antigens may play a role in the pathogenesis of this disease in some cases.     

Induction of IgA against Haemophilus parainfluenzae antigens in tonsillar mononuclear cells from patients with IgA nephropathy

Much evidence suggests that IgA production in vivo and in vitro is enhanced in patients with IgA nephropathy (IgAN). We have demonstrated glomerular deposition of the outer membranes of Haemophilus parainfluenzae (HP) antigens (OMHP) and the presence of HP-specific IgA in the serum of patients with IgAN. In this study, we investigated the production of IgA and several cytokines by tonsillar mononuclear cells (TMC) from IgAN patients induced by stimulation with OMHP. The spontaneous production of total IgA and TGF-beta by TMC from IgAN patients was higher than that by TMC from patients with chronic tonsillitis (CT) (P < 0.05). Stimulation with OMHP in vitro enhanced the production of HP-specific IgA by TMC from IgAN patients (P < 0.01), but not by TMC from CT patients. OMHP stimulation also enhanced the production of TGF-beta and IL-10 by TMC from IgAN patients (P < 0.001). These results suggest that the infection of HP in the tonsil may be involved in the etiology of IgAN.     

Comparison of three commercial test systems for biotyping Haemophilus influenzae and Haemophilus parainfluenzae

The biotypes of Haemophilus influenzae and Haemophilus parainfluenzae isolates were determined with three commercially available biochemical test kits: the IDS RapID NH system, the Neisseria-Haemophilus identification test (NHI card), and the API NH strip. The API NH strip performed best, correctly classifying the biotypes of 371 of 380 (97.6%) different challenge strains.     

IgA nephropathy

This presentation attempts, to define the criteria for diagnosis of the suggested clinicopathologic entity of IgA nephropathy. Of 250 patients in whom renal biopsies with immunofluorescence, light and electron microscopic, and clinical data were available, 12 patients (4.8 per cent) showed predominance of IgA with localization mainly in the mesangium, a variable degree of mesangial cell proliferation, and increased mesangial matrix on light microscopy. Electron densities were restricted to the mesangium and paramesangial areas. IgA was accompanied by C3 only in two patients, by IgG and C3 in five, and by IgG, IgM, and C3 in five. Properdin was found in 11 of these 12 cases. There was a marked male predominance. All showed gross or microscopic hematuria and variable proteinuria. Ten had had normal renal function tests at the time of presentation, and there was no significant worsening of renal function in the 11 patients followed for six to 84 months after biopsy. No morphologic change was detected in two repeat biopsies six and seven years after the initial biopsies. These 12 patients appear to form a distinct clinicopathologic entity. They can only be separated from other glomerular disorders with IgA when the morphologic and clinical findings are considered in combination with the finding of diffuse IgA predominance on renal biopsy.     

IgA nephropathy

Conclusion IgA nephropathy is a frequent disease, reported in almost every country in the world, which appears early in the life of males rather than females. It is readily diagnosed by immunofluorescence analysis of a renal biopsy. Its benign reputation begins to fade as more cases of rapid evolution towards renal failure are reported.Much has been learned about the various forms of IgAN in the past 15 years, yet complete understanding of the disease mechanism eludes us. Many clinicians and immunologists, however, continue the investigation, which will hopefully soon bring more complete answers and good news for the patients.     

Haemophilus parainfluenzae Liver Abscess after Successful Liver Transplantation

Haemophilus parainfluenzae was isolated from a bile specimen and from an aspirate of a liver abscess in a 58-year-old liver-transplanted woman that was indicative of an invasion of the graft by an ascending route. Drug therapy, immunosuppression, rejection therapy, and Roux-en-Y choledochojejunostomy may have contributed to the septic course. Interdisciplinary cooperation was instrumental in diagnosis and successful management in this case.     

Coexistence of IgA nephropathy and membranous nephropathy

Renal biopsy findings of a 27-year-old female with asymptomatic proteinuria and hematuria revealed two distinct glomerular alterations compatible with both IgA nephropathy and membranous nephropathy. The concomitant presence of two different primary glomerular diseases is very rare.     

Isolation of Haemophilus influenzae and Haemophilus parainfluenzae from genital-tract specimens with a selective culture medium

A series of 2027 genital tract specimens was cultured for Haemophilus species on non-selective chocolate agar and on a selective medium (Choc-VBCA). The latter gave a significantly higher isolation rate. H. influenzae was isolated from 27 specimens and H. parainfluenzae from 81 specimens by use of the selective medium. The biotype distribution of both species was compared with that of an equal number of isolates from respiratory-tract secretions. H. influenzae biotypes II and IV were found to predominate in genital strains and biotypes II and III in respiratory strains. With H. parainfluenzae, biotype II was most frequent in both sites. Two new biotypes of H. parainfluenzae (VI and VII) are described. The significance of the use of selective media and of biotype distribution are discussed.     

New satellitism test for isolation and identification of Haemophilus influenzae and Haemophilus parainfluenzae in sputum.

A new satellitism test designed to facilitate the isolation and identification of Haemophilus influenzae and Haemophilus parainfluenzae is described. In the basal medium, nicotinamide adenine dinucleotide is incorporated at a concentration of 0.2 mug per ml, an amount adequate for H. influenzae but not for H. parainfluenzae. Two disks are placed on the surface of the medium, one disk being impregnated with 60 mug of hemin and the other with 15 mug of nicotinamide adenine dinucleotide. Under these conditions, H. influenzae strains grow around the hemin disk only and the majority of H. parainfluenzae grow around the nicotinamide adenine dinucleotide disk. This procedure gives results which are more clear cut than other established methods, especially in sputum culture.     

Comparison of genital and respiratory carriage of Haemophilus parainfluenzae in men

In the first study, genital carriage of Haemophilus parainfluenzae was investigated in 103 women and 292 men attending a clinic for genitourinary medicine. In a second study, pairs of urethral and throat swabs were studied in 279 men. The vaginal carriage was 2%, urethral 12.4% and throat 13.3%. Biotype 2 was found to be a genital type and throat carriage of this biotype was significantly associated with its concomitant urethral carriage. Biotypes 1 and 3 were mainly found in the throat. Biotype 2 was significantly more likely to be resistant to ampicillin, tetracycline and sulphonamide but biotype 1 was significantly more likely to be resistant to trimethoprim.     

Urinary IgA in IgA nephropathy and Henoch-Schoenlein purpura

To determine the concentrations and molecular forms of urinary IgA in IgA nephropathy and Henoch-Schoenlein purpura, we studied 29 patients with these IgA-associated renal diseases (IgAN). Control groups comprised 10 patients with other diverse renal diseases and 11 healthy volunteers. Urinary IgA and IgG concentrations were higher in IgAN than in either control group and correlated positively with the serum creatinine concentration as well as the urinary protein excretion (P<0.01). However, IgA/IgG ratios did not differ among the three groups. Polymeric IgA (p-IgA) in the urine predominated only in normals; in IgAN and patients with other renal diseases, monomeric IgA (m-IgA) occurred almost exclusively. Serum IgA concentrations were generally normal in IgAN; four patients had concentrations greater than 500 mg/dl. Although the fraction of p-IgA in serum (median, 18%) was increased above normal (5–10%) in 13 of 16 (81%) subjects, neither the concentration of IgA or IgG nor the amount of p-IgA correlated with the serum creatinine concentration. These data suggest that the molecular form and concentration of urinary IgA are not discriminating for IgAN and are independent of these characteristics of serum IgA.     

Clustering of an outer membrane adhesin of Haemophilus parainfluenzae.

Haemophilus parainfluenzae synthesizes an outer membrane protein adhesin which mediates binding to oral streptococci, salivary pellicle, and neuraminidase-treated erythrocytes. An indirect gold labeling technique and immunoelectron microscopy verified the location of this outer membrane protein. Further, a clustering of gold particles was observed in irregular patches at the cell surface.