Concurrent antiglomerular basement membrane antibody and immune complex mediated glomerulonephritis

A teenage male, with Goodpasture's syndrome and serum antiglomerular basement membrane (anti-GBM) antibodies, had a focal proliferative glomerulonephritis with crescents. Immunofluorescence microscopy of his glomeruli using anti-IgG antibodies demonstrated both intense linear GBM staining, and granular subepithelial staining. Electron microscopy revealed numerous subepithelial electron-dense deposits. Identical IgG subclass restriction (dominance of IgG1 and IgG4) of both types of glomerular deposits in this patient supports, but does not prove, a postulate that the linear staining was due to anti-GBM antibodies bound to intact GBM, and that the granular staining was due to anti-GBM antibodies complexed with freed GBM antigens.     

Fatal pulmonary-renal syndrome manifested with immune complex crescentic glomerulonephritis in a patient with MPO-ANCA seropositivity

Recent reports have indicated that a significant number of immune complex glomerulonephritis (GN) cases are associated with antineutrophilic cytoplasmic antibody (ANCA). However, most of the reported cases were associated with underlying primary glomerular diseases. When primary glomerular diseases were not found, immune deposits tended to be non-specific and the level of ANCA is usually borderline. We report here upon a case of life-threatening pulmonary-renal syndrome manifested simultaneously with immune complex GN and myeloperoxidase (MPO)-ANCA seropositivity. A 29- year-old man was admitted with pulmonary hemorrhage and rapidly progressing renal dysfunction. On admission, ANCA revealed perinuclear staining with a titer of 1:160. The MPO-ANCA level was 59 IU by ELISA. Other serologic markers including ANA, anti-DS-DNA and anti-GBM Ab were negative. Renal biopsy showed cellular crescents in eight of 18 glomeruli. Immunofluorescence staining showed strong granular deposits of C3, C1q, IgG and IgM in the capillary loop and the mesangium. Electron microscopy showed multifocal electron dense deposits scattered in the mesangium, paramesangium, and the subendothelial and subepithelial areas. The patient initially responded to steroid and cyclophosphamide. MPO-ANCA decreased to less than 10 IU. Twenty three days after hospital discharge, the patient was re-admitted urgently with fever, generalized papulonodular skin lesions, and a recurrence of massive pulmonary hemorrhage and renal dysfunction. He died from uncontrolled pulmonary hemorrhage and respiratory insufficiency. P-ANCA titer and MPO-ANCA level at the second admission were 1:320 and 82 U/ml respectively. Interestingly, relapse was shown to be triggered by varicella zoster infection.     

Weber-Christian panniculitis with immune complex glomerulonephritis

The etiology of Weber-Christian panniculitis is unknown. A case is presented in which an association is found between immune complex glomerulonephritis and a relapse of Weber-Christian panniculitis. This case adds to the literature, implicating immune system dysfunction in the pathophysiology of this disease.     

A syndrome of immune complex glomerulonephritis and ophthalmic abnormalities

Two sibs (one male and one female) suffering from a combination of immune complex glomerulonephritis and various ophthalmologic disorders are presented. The two cases belong to a family in which the parents are not related and seven sibs are affected, three females and a male with the combination, and three males with severe ophthalmological changes and proteinuria. Clinically, case 2 had only ophthalmological manifestations but renal biopsy findings were similar to those of case 1, which could mean that all the others with eye abnormalities also had renal disease. Although there are several reports of combinations of eye and renal disorders, the sibs reported here do not fit into any of the known syndromes.     

Development of IgA nephropathy-like glomerulonephritis associated with Wiskott-Aldrich syndrome protein deficiency

Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder caused by mutations in the WAS gene. Glomerulonephritis is a frequent complication, however, histopathological data from affected patients is scarce because the thrombocytopenia that affects most patients is a contraindication to renal biopsies. We found that WASp-deficient mice develop proliferative glomerulonephritis reminiscent of human IgA nephropathy (IgAN). We examined whether increased aberrant IgA production is associated with the development of glomerulonephritis in WASp-deficient mice. Serum IgA and IgA production by splenic B cells was increased in WASp-deficient mice compared to wild-type (WT) mice. A lectin-binding study revealed a reduced ratio of sialylated and galactosylated IgA in the sera from old WASp-deficient mice. Circulating IgA-containing immune complexes showed significantly higher titers in WASp-deficient mice compared to WT mice. These results indicate that the increased IgA production and aberrant glycosylation of IgA may be critically involved in the pathogenesis of glomerulonephritis in WAS.     

Intrapulmonary hemorrhages and immune complex glomerulonephritis masquerading as Goodpasture's syndrome

The case of a patient who presented clinically with hemoptysis and was shown to have bilateral pulmonary infiltrates and renal abnormalities is described. This typical clinical setting was initially diagnosed as Goodpasture's syndrome. Open biopsies of lung and kidney were performed. Light microscopy failed to demonstrate the renal abnormalities most often associated with Goodpasture's syndrome. Immunofluorescence and electron microscopic findings were compatible with a diagnosis of immune complex glomerulonephritis. No immunologic lesions were demonstrated by lung biopsy. Antiglomerular basement membrane antibodies were not detected in the patient's serum. In view of the drastic prognostic and therapeutic consequences of Goodpasture's syndrome, it is essential that this diagnosis be confirmed by tissue examination and serologic testing.     

1例Wiskott-Aldrich综合征临床特征和致病基因突变分析

目的:分析1例Wiskott-Aldrich综合征患者的临床特征及分子遗传特征。方法:分析患者的临床特征,收集患者及其父母外周血,提取基因组DNA,针对WASP基因所有编码外显子及外显子和内含子交界处进行PCR扩增测序。结果:我们报道的患者具有典型的WAS表型,临床得分为5分;患儿Coomb’s试验,自身抗体中ANA及类风湿因子均阳性,伴有自身免疫性疾病。患儿为WASP基因第7外显子中第665位核苷酸C突变为T(c.665C>T),导致211位密码子发生无义突变,该位置提前出现终止密码(p.R211X);其母亲为此突变基因携带者。结论:这例男性中国Wiskott-Aldrich综合征患儿由于WASP基因突变致病,此基因型患儿(p.R211X)拥有典型的WAS表型且伴有自身免疫性疾病的临床型为国内首次报道。     

IgE and immune complex glomerulonephritis

A case is presented of immune complex proliferative glomerulonephritis associated with peripheral eosinophilia, renal deposits of IgE, and eosinophils in glomeruli and interstitial tissue. Two sequential renal specimens are described. This study also reviews prior reports of IgE in glomerulonephritis and discusses possible explanations for the presence of IgE.     

Novel variant in the KCNK9 gene in a girl with Birk Barel syndrome

Birk Barel syndrome also known as KCNK9 imprinting syndrome is a rare developmental disorder associated with a loss-of-function variant in KCNK9, an imprinted gene with maternal expression on the 8th chromosome encoding the TASK3 (TWIK-related acidity inhibited K + -channel 3). Only two variants of KCNK9 have been associated with this condition before, both of them leading to the same amino-acid exchange p.Gly236Arg (Barel, 2008, Graham, 2016). We describe a case of a 17-year-old girl presenting with very similar phenotype and pure motor neuropathy with a novel variant c.710C > A: p.Ala237Asp (NM_001282534.1) in KCNK9 found by whole exome sequencing. Our case suggests that Birk Barel syndrome may not be caused only by variants leading to amino-acid exchange p.Gly236Arg but also by other missense variant in this gene and that peripheral motor neuropathy might be a feature of this syndrome.     

Morphogenesis of immune complex glomerulonephritis]

Morphological changes in the kidneys in nonspecific ulcerative colitis were studied and the following variants of the kidney involvement were established: (1) allergic changes manifested by membraneous and mesangio-proliferative glomerulonephritis, renal vasculitis, phenomena of stromal desorganization with lymphoid and histiocyte infiltrations; (2) metabolic changes manifested by various kinds of degeneration of the tubular apparatus including changes typical of potassium-deficient nephropathy; (3) toxic -- necrotic nephrosis and (4) infectious -- nonsuppurative and suppurative interstitial nephritis.     

Congenital variant Rett syndrome in a girl with terminal deletion of chromosome 3p

A girl fulfilling four/five of six inclusion criteria and eight/nine of 11 supportive criteria for atypical Rett syndrome had a cytogenetic deletion of chromosome 3p, del(3)(pter-->3p25.1 approximately 25.2). The deletion was situated on the maternally derived chromosome and by molecular analysis the deletion breakpoint was shown to be between DNA markers D3S3589 and D3S1263.     

Triple-drug treatment of autologous immune complex glomerulonephritis

Autologous immune complex glomerulonephritis, an established experimental model of membranous glomerulopathy in man, has been used to investigate the effect of various drugs on its course. Because immunosuppressive or anti-inflammatory drugs are reported to have little or no effect on autologous immune complex glomerulonephritis a combination of cyclophosphamide, azathioprine and prednisolone was used in this study. Since in this glomerular disease free-circulating anti-FxlA antibody has pathogenetic significance special attention was paid to the effect of triple-drug treatment on the anti-FxlA serum titres and the relation between these titres, deposition of immune aggregates in the glomerular basement membrane and the occurrence of proteinuria. It was found that triple-drug treatment could prevent completely deposition of immune aggregates in the glomeruli as well as development of proteinuria when it was started simultaneously with the immunization procedure. If triple-drug treatment was started as the moment when immune deposits appeared along the glomerular basement membrane, a decrease in serum titre of autologous anti-FxlA antibody, diminished deposition of immune aggregates along basement membranes and a significant decrease of proteinuria were found. In later stages of the disease when proteinuria was fully developed, no beneficial effect of triple-drug treatment could be demonstrated. It is concluded that the beneficial effect of triple-drug treatment on early stages of autologous immune complex glomerulonephritis is caused by a decrease in the level of free-circulating anti-FxlA antibody.     

Immune complex glomerulonephritis mediated by thyroid antigens.

Hypothyroidism, microscopic hematuria, and proteinuria developed in an 11-year-old girl. A renal biopsy specimen showed increased mesangial cells and matrix with focal glomerular basement membrane thickening. Three years later, a pronounced increase in proteinuria was detected. Elevated levels of antibody to thyroid microsomal antigen and thyroglobulin were found in the serum. A renal biopsy specimen showed a pronounced increase in mesangial cells and matrix with generalized glomerular basement membrane thickening. Electron microscopic studies demonstrated granular deposits in the capillary walls and mesangium. Immunofluorescent studies revealed granular deposits of IgG, IgM, and C3, primarily on the glomerular basement membrane. By indirect immunofluorescence, granular glomerular basement membrane and mesangial staining were detected with antibody specific for thyroglobulin and thyroid microsomal antigen. These observations suggest development of immune complex glomerulonephritis mediated by thyroid antigens.     

国内首例Costello综合征患儿HRAS基因突变分析

目的 通过对1例临床疑似Costello 综合征的患者进行HRAS基因分析并确诊。方法 提取患者及其父母的基因组DNA,PCR扩增HRAS基因的第2～5个编码外显子并直接测序。Pubmed检索Costello综合征的临床表现、实验室检查和治疗干预方法。结果 在HRAS基因第2外显子34位碱基序列处发现一个已知错义突变c.34G>A,p.Gly12Ser。患者父母DNA未检测到相同突变。结论 Costello 综合征是一种罕见的常染色体显性遗传病,患者有特征性面容、极度喂养困难史和生长发育落后等,确诊有赖于HRAS基因突变分析。     

Identification of five novel WASP mutations in Chinese families with Wiskott-Aldrich syndrome

The Wiskott-Aldrich Syndrome (WAS) is an X-linked recessive immunodeficiency caused by mutation in the gene encoding WAS protein (WASP). The disease is characterized by eczema, thrombocytopenia and severe immunodeificency and is associated with extensive clinical heterogeneity. Mutation studies indicated that the mutated genotypes are also highly variable. In this study, we performed PCR-direct sequencing analysis of the WAS gene in six unrelated Chinese families. Five novel mutations identified, included two nonsense mutations (506C-->T, 1388-->T), a small insertion (685-686insCGCA) and two single-base deletions (384delT, 984delC). All of the mutations are predicted to lead to premature translational termination of WASP.