Although the origin of the immune complex depositions remained unknown without a kidney biopsy before IVIG supplements, our case raised the possibility that nephropathy can be an entity of autoimmune diseases in XLA

Although the origin of the immune complex depositions remained unknown without a kidney biopsy before IVIG supplements, our case raised the possibility that nephropathy can be an entity of autoimmune diseases in XLA. The goal of IVIG therapy in XLA is to maintain serum IgG levels at 500C800?mg/dL and prevent recurrent bacterial infections that could be life threatening [30,31]. bacterial infections Miquelianin since childhood, XLA was not diagnosed until B-lymphocyte surface antigen studies and a genetic analysis were conducted. Conclusions We suggest that B-lymphocyte surface antigen studies and a BTK mutation analysis should be performed in familial patients with selective IgM Miquelianin deficiency to rule out atypical XLA. Keywords: X-linked agammaglobulinaemia, Brutons tyrosine kinase, Proteinuria, Haematuria, Immunoglobulin Background X-linked agammaglobulinaemia (XLA) (OMIM # 300755) is a humoural immunodeficiency disease characterised by severe hypogammaglobulinaemia, defective B cell development, and extremely decreased numbers of mature B cells [1]. In 1952, Colonel Ogden Bruton described the first case of XLA in a boy with a history of recurrent bacterial infections [2]. The gene responsible for XLA was identified in 1993 and named Brutons tyrosin kinase (BTK) [3]. The gene is localised at Xq21.3-Xq22 and contains 19 exons spanning 37.5?kb [4]. A member of the Tec family, the gene is a cytoplasmic tyrosine kinase that plays a critical role in the development of B cells [5]. Five domains of BTK, comprising pleckstrin homology (PH), Tec homology (TH), Src homology 3 (SH3), Src homology 2 (SH2), and the kinase domain TK, have been identified, with each having a distinctive function [5]. The lack of functional BTK results in defective B cell development at the pro-B and pre-B cell stages [6], leading to a reduction of mature B cells in the peripheral blood. The clinical diagnosis of XLA depends on a positive family history of immunodeficiency, recurrent bacterial infections before the age of 5?years, life-threatening bacterial infections in early childhood, and considerably low levels of all isotypes of serum immunoglobulins [7]. These indications are necessary for a definite diagnosis of XLA: the patient must be male and have less than 2% CD19+ B cells with mutations in the gene, absent BTK mRNA on a northern blot analysis of neutrophils or monocytes, absent BTK proteins in monocytes or platelets, as well as maternal cousins, uncles, or nephews who have mutations [8]. Most XLA-afflicted boys were diagnosed with repeated or protracted bacterial infections during early childhood after their maternal immunoglobulins had been lost [9], and before the era of the intravenous immunoglobulin (IVIG) and antibiotics, the disease could be life threatening. Currently, only 2 XLA cases associated with nephropathies can be found in the literature [10,11]. Here, we report an atypical XLA case occurring with a novel mutation in a Chinese boy presenting with nephritis and selective IgM deficiency. Case presentation A 6-year-old Chinese boy with a 2-year history of persistent haematuria and proteinuria found by routine screen was referred to our department. He had suffered several episodes of otitis media and maxillary sinusitis since the age of 3?years without requiring hospitalisation. He was diagnosed with selective IgM deficiency at the age of 5?years. Clinical examinations revealed a normal gross appearance and growth percentile, and there was no pitting edema or skin rash. His family history was unremarkable except that his elder brother, who had experienced recurrent sinusitis and atopic dermatitis, had been diagnosed with selective IgM deficiency at the age of 3?years. His brother had received intravenous immunoglobulin (IVIG) treatments and has normal renal function without proteinuria and haematuria. Examining our patients kidneys by using ultrasound exposed that his kidneys and urinary tract system were grossly normal. Performing a dipstick urinalysis exposed the urine contained occult blood 3+ and protein 2+. His daily protein loss was 1.4?g/d. Additional blood and urine biochemistry data, including titres of the antinuclear antibodies, antistreptolysin-O, and autoantibodies related to systemic lupus erythematosus were all bad (Table? 1). Table 1 ATP1A1 Clinical characteristics of our individuals with X-linked agammaglobulinemia gene exposed that the patient and his brother both exhibited a c.347C?>?T (p.P116L) mutation inherited using their mother (Number? 3). After a 2-yr follow up, our patient remains proteinuria-free with normal kidney function and no infections. Written educated consent was acquired for the subjects included in this study and was authorized by the Kaohsiung Medical University or college Hospital Institutional Review Table. The research sequences for the gene are NG_009616.1 and NM_000061.2. Open in a separate window Number 1 Immunofluorescence microscopy showed strong staining of (A) IgG, (B) Miquelianin IgA, (C) C3, (D) IgG kappa, and (E) IgG lambda over mesangium and glomerular basement.