Manejo del síndrome de transfusión feto fetal en pandemia COVID-19: reporte de caso

El síndrome de transfusión feto-fetal (STFF) es una complicación propia de los embarazos gemelares monocoriales, con mortalidad perinatal del 80 a 100%. Ocurre por un desequilibrio en el flujo sanguíneo placentario entre ambos gemelos. El diagnóstico se basa en la discordancia del líquido amniótico y luego se clasifica en estadios según los criterios de Quintero. El tratamiento principal es la fetoscopia y fotoablación con energía láser (FFL) de las anastomosis placentarias. Presentamos un caso de gestación gemelar monocorial biamniótica tratado con FFL en plena cuarentena e inmovilización de la pandemia COVID-19 en Perú, que incluyó diagnóstico oportuno y referencia rápida para recibir el tratamiento especializado.

The twin-to-twin transfusion syndrome (TTTS) is a potentially lethal complication that can occur in monochorionic twin pregnancies due to an imbalance in placental blood flow. Diagnosis is based on amniotic fluid discordance and classified using the Quintero staging system. The primary treatment is fetoscopic laser photocoagulation (FLP) of placental anastomoses. A successful case of FLP treatment in a monochorionic diamniotic twin pregnancy with TTTS during COVID-19 pandemic in Peru is presented.

Ly9 (CD229) Antibody Targeting Depletes Marginal Zone and Germinal Center B Cells in Lymphoid Tissues and Reduces Salivary Gland Inflammation in a Mouse Model of Sjögren's Syndrome.

Sjögren's Syndrome (SjS) is a common chronic autoimmune disease characterized by the B cell hyperactivation, lymphocyte infiltration, and tissue damage of exocrine glands. It can also present life-threatening extraglandular manifestations, such as pulmonary and hepatic involvement, renal inflammation and marginal zone (MZ) B cell lymphoma. Several biologic agents have been tested in SjS but none has shown significant efficacy. Here, we report the effects of Ly9 (CD229) antibody targeting, a cell surface molecule that belongs to the SLAM family of immunomodulatory receptors, using NOD.H-2h4 mice as a model of SjS-like disease. Female mice were treated with anti-Ly9 antibody or isotype control at week 24, when all mice present SjS related autoantibodies, salivary gland infiltrates, and marginal zone (MZ) B cell pool enlargement. Antibody injection depleted key lymphocyte subsets involved in SjS pathology such as MZ, B1, and germinal center B cells in spleen and draining lymph nodes without inducing a general immunosuppression. Importantly, mice receiving anti-Ly9 mAb showed a reduced lymphocyte infiltrate within salivary glands. This reduction may be, in part, explained by the down-regulation of L-selectin and alfa4/beta7 integrin induced by the anti-Ly9 antibody. Furthermore, levels of anti-nuclear autoantibodies were reduced after anti-Ly9 treatment. These data indicate that Ly9 is a potential therapeutic target for the treatment of SjS.

Expression profiles of novel cell surface molecules on B-cell subsets and plasma cells as analyzed by flow cytometry.

Cell surface molecules are present on several lymphocyte subsets and are differentially expressed during lymphocyte development and activation. Human Leukocyte Differentiation Antigen (HLDA) Workshops have played an essential role in the identification and characterization of the molecules found in the membrane of hematopoietic cells. In the present study, the reactivities of sixty-five monoclonal antibodies (mAbs) submitted to the HLDA9 Workshop were tested. A multicolor flow cytometric analysis was performed in order to determine the expression profiles of these proteins on peripheral blood lymphocytes, hematopoietic cell lines, and tonsil B-cells. The following B-cell subsets were assessed: mature naïve, pre-germinal center, germinal center, unswitched and switched memory, plasmablasts, and plasma cells. Immunohistochemical analysis on formalin-fixed paraffin-embedded tonsils was also carried out. Remarkably, a large group of immunoglobulin family inhibitory cell surface molecules were observed on several distinct B-cell subsets including: CD152 (CTLA4), CD170 (Siglec-5), CD272 (BTLA), CD305 (LAIR1), CD307d (FCRL4), and CD329 (Siglec-9). The following molecules were also found to be differentially expressed on B-cell subsets (CD80, CD185 (CXCR5), CD196 (CCR6), CD270 (TNFRSF14), CD307a-c (FCRL1-3), CD319 (SLAMF7) and CD362 (SDC2)) or delineated B-cell subpopulations (CD126 (IL-6R), CD255 (TNFSF12), CD264 (TNFRSF10D), CD267 (TNFRSF13B) and CD329 (Siglec-9)). Of these, only CD307a, CD307b, and CD307d presented a B-cell-specific expression pattern. Our results show that several of these molecules are capable of further subdividing the known B-cell subsets and, in fact, may represent new markers for research, diagnosis, and eventually targets for the treatment of B-cell malignancies and autoimmune diseases.

Immunohistochemical analysis of HLDA9 Workshop antibodies against cell-surface molecules in reactive and neoplastic lymphoid tissues.

The study of human leukocyte antigens, predominantly by monoclonal antibody (mAb) techniques, has become a fundamental part of basic research and clinical investigation. In particular, mAbs have allowed a more precise phenotypic dissection of lymphocyte subsets and have increased our understanding of the mechanisms that regulate humoral immunity and tumour transformation. In the present study we have investigated the expression, in both reactive and neoplastic lymphoid tissues, of a panel of HLDA9 mAbs (TRAIL-R2 (CD262), CCR6 (CD196), HVEM (CD270), Galectin-3 and BAFF-R (CD268)) capable of recognizing their target molecules in paraffin-embedded tissue sections. A series of reactive lymphoid tissues and B and T cell lymphomas (151 cases) were studied, using whole sections and tissue microarrays (T.M.A.). The most interesting results were obtained from the Galectin-3 study. In human lymphomas our data are consistent with the results previously described that showed that Galectin-3 is expressed in anaplastic large cell lymphoma (ALCL). Moreover, we provide additional information of Galetin-3 expression in other lymphoma types. In T cell lymphomas, Galectin-3 was strongly expressed by a significant number of peripheral (PTCL 12/43) and cutaneous T cell lymphomas (CTCL 6/24) while in B cell lymphoma only a small proportion of follicular (FL 2/10) and diffuse large B cell lymphomas (DLBCL 3/10) were positives. Our study encourage further investigations into the potential role that TRAIL-R2, CD196, HVEM, Galectin-3 and BAFF-R proteins may play in lymphocyte development and differentiation, but also constitute an additional tool for the study of lymphoid subpopulations and lymphoproliferative disorders.

New B-cell CD molecules.

B cells not only play a pivotal role in humoral immunity, but also are involved in a broad spectrum of immune responses, including antigen presentation and T-cell function regulation. The identification of cell-surface CD molecules derived from a series of Human Leukocyte Differentiation Antigens (HLDA) Workshops has been instrumental to the discovery and functional characterization of human B-cell populations. Moreover, many events regulating B-cell development, activation, and effector functions are orchestrated by these cell-surface molecules. During the Ninth HLDA Workshop (HLDA9) eighteen new CDs were allocated to cell-surface molecules expressed on B cells: CD210a (IL10RA), CD215 (IL15RA), CD270 (TNFRSF14), CD307a (FCRL1), CD307b (FCRL2), CD307c (FCRL3), CD307d (FCRL4), CD351 (FCAMR), CD352 (SLAMF6), CD353 (SLAMF8), CD354 (TREM1), CD355 (CRTAM), CD357 (TNFRSF18), CD358 (TNFRSF21), CD360 (IL21RA), CD361 (EVI2B), CD362 (SDC2), and CD363 (S1PR1). Here we present their expression patterns on leukocytes, including T lymphocytes, NK cells, granulocytes, monocytes, plasmacytoid and monocyte-derived dendritic cells, and several B-cell subsets. These new CD molecules are expressed on B cells at various stages of differentiation; from bone marrow precursor pro-B cells to plasma cells. Three of them, CD307a, CD307b and CD307d, exhibit a B-cell restricted expression pattern, whereas the rest are also present on other leukocytes. In this paper we also review the structural characteristics, expression, and function of these new CD molecules. The availability of monoclonal antibodies directed against novel B cell-surface molecules will have broad implications not only for B-cell biology, but also for the development of new diagnostic and therapeutic tools.