Immunophenotyping in peripheral blood mononuclear cells, aqueous humour and vitreous in a Blau syndrome patient caused by a novel NOD2 mutation

Abstract

The genetic and immunophenotypic characteristics of a 3-year-old patient with Blau syndrome (BS), an early onset sarcoidosis caused by mutations in NOD2, were investigated. Molecular analysis of NOD2 gene was achieved by PCR and direct nucleotide sequencing. Immunophenotyping included cytometric analysis of memory-effector markers on T-cells, and cytokine in serum, aqueous humour and vitreous. A novel M513R mutation in NOD2 was demonstrated. Immunophenotyping revealed higher frequency of CCR4+ cells and CCR9+ cells on CD4+ cells; most CD8+ cells were CCR7- and CCR9+. IL6 and IL-8 were detected in a gradient manner: vitreous humour>aqueous humour>serum. The immunophenotype in this patient was characterized by a differential expression of chemokine receptors on T cells and by a particular ocular microenvironment enriched in IL-6 and IL-8. To our knowledge, this is the first study analysing the immunological features of BS at aqueous humour, vitreous and blood levels. Our results expand the knowledge of the genetic and immunopathological basis of BS.

Autoinflammatory granulomatous diseases: from Blau syndrome and early-onset sarcoidosis to NOD2-mediated disease and Crohn's disease

“…Renal involvement in the form of bilateral nephritis, nephrocalcinosis and chronic renal failure has also been observed. 11 21 22 37 In several cases, the granulomatous pattern of nephritis has been confirmed by biopsy. 22 38 The coexistence of renal cell carcinoma has been described in a Turkish patient with BS with the R334Q mutation, but it has not been clearly related to the disease.…”

Blau syndrome revisited

“…The first studies for each mutation [9,10,12,13,29,[32][33][34][35][36] are listed on the right column of Table 1, followed by any subsequent studies for that particular mutation [10][11][12][13][14][15]20,28,29,[37][38][39][40][41][42]. From a total of 67 independent occurrences (i.e.…”

Caveats and truths in genetic, clinical, autoimmune and autoinflammatory issues in Blau syndrome and early onset sarcoidosis

“…Arterial hypertension has often been described [60,72]. Renal involvement in the form of bilateral glomerulopathy [83], renal calcification [80] and chronic renal failure [64,72] has been observed in BS, while the granulomatous origin of nephritis has been demonstrated histologically on renal biopsies in many cases [65,72]. Medullary nephrocalcinosis has also been reported in EOS [78].…”

“…Despite the increasing use of genetic testing, the real prevalence of BS and EOS remains unknown: both familial and sporadic forms have been reported in Caucasians [46,55,70,85,98], Spanish [72], Asian [47,51,69,87], and American [61,75,83] individuals. Rough incidence data could be derived from analysis of a total of 48 Danish childhood-onset sarcoidosis patients, obtained from a nationwide patient registry during the period 1979-1994, and estimating that sarcoidosis incidence per 100,000 person/year was 0.06 for children under 5 and 0.10 for those between 5 and 9 years of age.…”