French practical guidelines for the diagnosis and management of AA amyloidosis.

AA amyloidosis is secondary to the deposit of excess insoluble Serum Amyloid A (SAA) protein fibrils. AA amyloidosis complicates chronic inflammatory diseases, especially chronic inflammatory rheumatisms such as rheumatoid arthritis and spondyloarthritis; chronic infections such as tuberculosis, bronchectasia, chronic inflammatory bowel diseases such as Crohn's disease; and auto-inflammatory diseases including familial Mediterranean fever. This work consists of the French guidelines for the diagnosis workup and treatment of AA amyloidosis. We estimate in France between 500 and 700 cases in the whole French population, affecting both men and women. The most frequent organ impaired is kidney which usually manifests by oedemas of the lower extremities, proteinuria, and/or renal failure. Patients are usually tired and can display digestive features anf thyroid goiter. The diagnosis of AA amyloidosis is based on detection of amyloid deposits on a biopsy using Congo Red staining with a characteristic green birefringence in polarized light. Immunohistochemical analysis with an antibody directed against Serum Amyloid A protein is essential to confirm the diagnosis of AA amyloidosis. Peripheral inflammatory biomarkers can be measured such as C Reactive protein and SAA. We propose an algorithm to guide the etiological diagnosis of AA amyloidosis. The treatement relies on the etiologic treatment of the undelying chronic inflammatory disease to decrease and/or normalize Serum Amyloid A protein concentration in order to stabilize amyloidosis. In case of renal failure, dialysis or even a kidney transplant can be porposed. Nowadays, there is currently no specific treatment for AA amyloidosis deposits which constitutes a therapeutic challenge for the future.

Autoimmune polyendocrine syndrome type 1 in north-western France: AIRE gene mutation specificities and severe forms needing immunosuppressive therapies.

BACKGROUND: Autoimmune polyendocrine syndrome type 1 (APS1) has been poorly evaluated in France. We focused on the north-western part of the country to describe clinical phenotypes, especially severe forms of the disease, and AIRE gene mutations. METHODS: Clinical and immunological data were collected, and pathological mutations were identified by DNA sequencing. RESULTS: Nineteen patients were identified with APS1. Clinical manifestations varied greatly, showing 1-10 components. Mucocutaneous candidiasis, adrenal failure, hypoparathyroidism, alopecia and other severe infections were the most frequent components. Four patients had severe forms, needing immunosuppressive therapy: 2 for hepatitis; 1 for severe malabsorption, and 1 for a T cell large granular lymphocytic leukemia. These therapies were very effective but caused general discomfort. One patient died of septicemia. Four different AIRE gene mutations were identified, and a 13-bp deletion in exon 8 (c.967-979del13) was the most prevalent. There was at least one allele correlating with this mutation and alopecia occurrence (p = 0.003). No novel mutation was detected. CONCLUSION: APS1 appears to be rare in north-western France. We identified 4 cases with a severe form needing immunosuppressive therapy. The AIRE gene mutations are more like those found in north-western Europe than those found in Finland.

Predominant Th1 and cytotoxic phenotype in biopsies from renal transplant recipients with transplant glomerulopathy.

Transplant glomerulopathy (TGP) appears to be a pathogenic feature of chronic antibody-mediated rejection, but the pathogenesis of this histologic entity is still poorly understood. Previous studies suggest the involvement of lymphocytes but the phenotypes of these cells have never been analyzed. Here, we report the first study of mRNAs for specific markers of CD4+ T cells including Th1 (T-bet and INFgamma), Th2 (IL4 and GATA3), Treg (Foxp3) and Th17 (IL-17 and RORgammat) subsets, cytotoxic CD8 T cells (Granzyme B) and B-cell markers (CD20) in renal biopsies from renal transplant recipients suffering interstitial fibrosis and tubular atrophy (IF/TA) with or without TGP but with a similar inflammatory score and controls including transplant recipients with normal renal function. Only INFgamma, T-bet (both functionally defined markers of Th1 CD4 T cells) and granzyme B (a CD8 cytotoxic marker) were significantly more strongly expressed in patients with TGP than in patients without TGP and normal controls. These results indicate a role of an active T-mediated inflammatory and cytotoxic process in the pathogenesis of TGP.

Heterogeneity of protein kinase C beta(2) expression in lymphoid malignancies.

AIMS: Protein kinase C (PKC) beta is an important regulator of lymphoid survival and its expression has been shown to be altered in lymphomas. The aim was to determine the expression of PKC beta(2) in various subtypes of lymphoproliferative diseases by immunohistochemistry. METHODS AND RESULTS: One hundred and forty archival samples representing various subtypes of lymphoproliferative diseases were analysed. Certain subtypes, such as mantle cell, lymphocytic or follicular lymphoma, were found to express PKC beta(2) in > 90% of the samples. In follicular lymphomas, the follicular lymphomatous areas were constantly labelled, whereas residual germinal centres remained negative. In follicular hyperplasia, PKC beta(2)+ cells were found in the mantle and marginal zones. Most angioimmunoblastic T-cell lymphomas, lymphoblastic T-cell lymphomas and marginal zone/mucosa-associated lymphoid tissue (MALT) lymphomas were labelled with anti-PKC betaII antibody, but the pattern of expression was more heterogeneous in these subtypes. A minority of diffuse large B-cell lymphomas were stained and most plasma cell malignancies were negative. None of the cases of Hodgkin's disease and anaplastic large cell lymphoma expressed PKC beta(2). CONCLUSIONS: PKC beta(2) expression varies significantly among lymphoproliferative diseases. In our series, the highest level of expression was found in mantle cell lymphomas and chronic lymphocytic lymphoma.

Post-traumatic fibro-osseous lesion of the ribs: a relatively under-recognised entity.

AIM: To report the description of a rare benign osseous lesion affecting the ribs entitled post-traumatic fibro-osseous lesion (PTFOL). METHODS: Seven cases of PTFOLs were retrieved from the archives of the University Hospital of Lille. Histological slides were reviewed and lesions were classified according to the histological patterns described by McDermott et al. Clinical and follow-up data were obtained from the patients' charts. RESULTS: PTFOLs occurred principally in men (mean age 31.8 years) with a known or suspected previous chest injury for four of them. No previous cancer was noted. Radiologically, PTFOLs readily presented as an isolated expansive lucency with a sclerotic rim located on the last five ribs. A constant increased uptake of radionucleotide was noted on bone scan. Microscopically, two fibro-osseous, four xanthomatous and one mixed pattern were individualised. Lesions were characterised by a network of anastomosing bone trabeculae without osteoblast lining within a fibrous stroma. A zonal maturation from woven to peripheral lamellar bone was characterised. Central sheets of lipid-laden histiocytes were conspicuous in the xanthomatous type. For each patient, clinical follow-up was excellent, without any recurrence. CONCLUSIONS: This is the second largest series of PTFOLs, which is considered to be a dysplastic healing process after trauma. It may be symptomatic or shown by imaging studies realised for unrelated reason. PTFOL is regularly misdiagnosed with other more common lesions of the ribs, such as fibro-osseous dysplasia, osteoma osteoid and benign fibrous histiocytoma. Its recognition is of importance because no follow-up is needed after resection.