RESUMEN
A20 Haploinsufficiency (HA20) is a monogenic autoinflammatory disease associated with an autosomal dominant mutation in the TNFAIP3 gene. It induces a defect in the inactivation of the pro-inflammatory NF-κB pathway. Less than 200 cases have been described worldwide. The clinical picture of the disease is essentially based on the association of recurrent fever and/or biologic inflammatory syndrome, aphtosis, often bipolar, and cutaneous folliculitis. However, the clinical spectrum of HA20 is very broad, including gastrointestinal (mainly colonic ulceration), articular, cutaneous, pericardial and lymph node involvement, as well as frequent association with organ-specific or non-specific autoimmune manifestations and/or autoantibodies, including antinuclear antibodies and anti-dsDNA. As a result, the diagnosis of a number of systemic or organic disorders, most notably Behçet's disease, Crohn's disease, and sometimes even systemic lupus, has been corrected to HA20 by molecular research for a heterozygous mutation with functional deficiency of TNFAIP3. Although the first signs of the disease often appear in the first years of life, the diagnosis is often made in adulthood and requires the involvement of both paediatric and adult physicians. Treatment for HA20 is not codified and relies on conventional or biological immunomodulators and immunosuppressants adapted to the patient's symptomatology. This review highlights the enormous diagnostic challenges in this autoinflammatory disease.
Asunto(s)
Haploinsuficiencia , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa , Humanos , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/genética , Mutación , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/genética , Enfermedades Autoinflamatorias Hereditarias/diagnóstico , Enfermedades Autoinflamatorias Hereditarias/genéticaRESUMEN
Some common clinical situations, such as splenomegaly or lymphocytosis, or less common, such as autoimmune hemolytic anemia, cold agglutinin disease, or cryoglobulinemia can lead to the diagnosis of splenic lymphoma. Splenic lymphoma is rare, mainly of non-hodgkinian origin, encompassing very different hematological entities in their clinical and biological presentation from an aggressive form such as hepato-splenic lymphoma to indolent B-cell lymphoma not requiring treatment such as marginal zone lymphoma, the most frequent form of splenic lymphoma. These entities can be challenging to diagnose and differentiate. This review presents different clinical and biological manifestations suspicious of splenic lymphoma and proposes a diagnosis work-up. We extended the strict definition of splenic lymphoma (lymphoma exclusively involving the spleen) to lymphoma thant can be revealed by a splenomegaly and we discuss the differential diagnosis of splenomegaly.
Asunto(s)
Anemia Hemolítica Autoinmune , Linfocitosis , Linfoma de Células B de la Zona Marginal , Neoplasias del Bazo , Anemia Hemolítica Autoinmune/diagnóstico , Anemia Hemolítica Autoinmune/terapia , Diagnóstico Diferencial , Humanos , Linfocitosis/patología , Linfoma de Células B de la Zona Marginal/diagnóstico , Linfoma de Células B de la Zona Marginal/patología , Linfoma de Células B de la Zona Marginal/terapia , Neoplasias del Bazo/diagnóstico , Neoplasias del Bazo/patología , Neoplasias del Bazo/terapia , Esplenomegalia/diagnóstico , Esplenomegalia/etiologíaRESUMEN
Preclinical models and clinical studies have shown that anti-CD20-based treatment has multifaceted consequences on T-cell immunity. We have performed a prospective study of peripheral T-cell compartment in FL patients, all exhibiting high tumor burden and receiving rituximab-chemotherapy-based regimen (R-CHOP). Before treatment, FL patients harbor low amounts of peripheral naive T cells, but high levels of CD4+ TEM, CD4+ Treg and CD8+ TEMRA subsets and significant amounts of CD38+ HLA-DR+ activated T cells. A portion of these activated/differentiated T cells also expressed PD-1 and/or TIGIT immune checkpoints. Hierarchical clustering of phenotyping data revealed that 5/8 patients with only a partial response to R-CHOP induction therapy or with disease progression segregate into a group exhibiting a highly activated/differentiated T cell profile and a markedly low proportion of naive T cells before treatment. Rituximab-based therapy induced a shift of CD4+ and CD8+ T cells toward a central memory phenotype and of CD8+ T cells to a naive phenotype. In parallel, a decrease in the number of peripheral T cells expressing both PD-1 and TIGIT was detected. These observations suggest that the standard rituximab-based therapy partially reverts the profound alterations observed in T-cell subsets in FL patients, and that blood T-cell phenotyping could provide a better understanding of the mechanisms of rituximab-based treatment.