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Background: Since the late '90s, infliximab (Remicade®) is being used successfully to treat patients with several non-infectious immune mediated inflammatory diseases (IMIDs). In recent years, infliximab biosimilars, including Remsima® were introduced in clinical practice. Aim: To investigate the interchangeability of Remicade® (originator infliximab) and its biosimilar Remsima® in patients with rare immune-mediated inflammatory diseases (IMIDs). Methods: This two-phased prospective open label observational study was designed to monitor the transition from Remicade® to Remsima® in patients with rare IMIDs. All included patients were followed during the first 2 years. The primary endpoint was the demonstration of non-difference in quality of life and therapeutic efficacy, as measured by parameters including a safety monitoring program, physicians perception of disease activity (PPDA) and patient self-reported outcomes (PSROs). Secondary outcomes included routine blood analysis, pre-infusion serum drug concentration values and anti-drug antibody formation. Results: Forty eight patients treated with Remicade® were switched to Remsima® in June-July 2016 and subsequently monitored during the first 2 years. The group consisted of patients with sarcoidosis (n = 17), Behçet's disease (n = 12), non-infectious uveitis (n = 11), and other diagnoses (n = 8). There were no significant differences in PPDA, PSROs, clinical and laboratory assessments and pre-infusion serum drug concentrations between the groups. De novo anti-drug antibodies were observed in two patients. Seven patients with sarcoidosis and five with another diagnosis developed a significant disease relapse (n = 7) or adverse events (n = 5) within 2 years; 10 of these patients discontinued Remsima® treatment, one withdrew from the study and one received additional corticosteroid therapy. Conclusions: We observed no significant differences in PSROs, PPDA and laboratory parameters after treatment was switched from Remicade® to Remsima®. However, disease relapse or serious events were observed in 12 out of 48 patients when treatment was switched from Remicade® to Remsima®. The choice to switch anti-TNF alpha biologics in patients with rare IMIDs, particularly in sarcoidosis, requires well-considered decision-making and accurate monitoring due to a possibly higher incidence of disease worsening.
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PURPOSE: Thyroid-stimulating hormone receptor (TSHR) stimulating autoantibodies are associated with Graves' ophthalmopathy (GO), the orbital manifestation of Graves' disease (GD). TSHR autoantibody levels and orbital TSHR expression levels correlate positively with GO disease activity. Platelet-derived growth factors (PDGF) are increased in GO and potently activate orbital fibroblast effector functions. We investigated the possible relationship between PDGF and TSHR expression on orbital fibroblasts and how that influences the immunopathological effects of TSHR autoantibodies on orbital fibroblast activity. METHODS: Orbital fibroblasts were stimulated with PDGF-AA, PDGF-AB, and PDGF-BB, and TSHR expression was determined by flow cytometry. Stimulatory effects of bovine TSH and GD immunoglobulins on orbital fibroblasts (with or without PDGF-BB preincubation) were determined by IL-6, IL-8, chemokine (C-C motif) ligand (CCL)-2, CCL5, CCL7, and hyaluronan ELISA. The TSHR blocking antibody K1-70 and the cAMP inhibitor H89 were used to determine involvement of TSHR signaling. RESULTS: PDGF-AB and PDGF-BB stimulation increased TSHR expression on orbital fibroblasts, whereas PDGF-AA did not. Furthermore, stimulation with bovine TSH and immunoglobulins from GD patients induced IL-6, IL-8, CCL2, and hyaluronan production by orbital fibroblasts, and PDGF-BB preincubation enhanced this response of orbital fibroblasts. Blocking studies with a TSHR blocking antibody and a cAMP inhibitor inhibited these effects, indicating the involvement of TSHR signaling and thus of TSHR stimulating autoantibodies herein. CONCLUSIONS: These findings indicate that PDGF-B containing PDGF isoforms amplify the immunopathological effects of TSHR-stimulating autoantibodies in GO patients by stimulating TSHR expression on orbital fibroblasts.
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Oftalmopatía de Graves/inmunología , Oftalmopatía de Graves/metabolismo , Inmunoglobulinas Estimulantes de la Tiroides/inmunología , Factor de Crecimiento Derivado de Plaquetas/farmacología , Receptores de Tirotropina/inmunología , Autoanticuerpos/inmunología , Autoanticuerpos/metabolismo , Becaplermina , Células Cultivadas , AMP Cíclico/metabolismo , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Fibroblastos/fisiología , Oftalmopatía de Graves/cirugía , Humanos , Ácido Hialurónico/metabolismo , Inmunoglobulina G/farmacología , Inmunoglobulinas Estimulantes de la Tiroides/genética , Factor I del Crecimiento Similar a la Insulina/farmacología , Interleucina-6/metabolismo , Órbita/patología , Órbita/cirugía , Proteínas Proto-Oncogénicas c-sis/farmacología , Receptor IGF Tipo 1/genética , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Tirotropina/farmacologíaRESUMEN
PURPOSE: Platelet-derived growth factors (PDGF) are regulators of fibroblast activity that may be involved in the pathophysiology of Graves' ophthalmopathy (GO). We unraveled the expression and origin of PDGF family members in GO orbital tissue and investigated the effect of PDGF isoforms on IL-6 and hyaluronan production and proliferation by orbital fibroblasts. METHODS: PDGF-A, PDGF-B, PDGF-C, PDGF-D, PDGF-Rα, and PDGF-Rß expression was determined by real-time quantitative PCR and PDGF-A and PDGF-B protein expression was determined by Western blot in orbital tissues. Orbital tissues were immunohistochemically stained for PDGF-A and PDGF-B expression, together with stainings for T cells, monocytes, B cells, macrophages, and mast cells. Effects of PDGF-AA, PDGF-AB, and PDGF-BB on orbital fibroblast proliferation and IL-6 and hyaluronan production were examined. Finally, effects of PDGF-BB- and PDGF-AA-neutralizing antibodies on IL-6 and hyaluronan production in GO whole orbital tissue cultures were tested. RESULTS: GO orbital tissue showed increased PDGF-A and PDGF-B mRNA and protein levels. Increased numbers of PDGF-A- and PDGF-B-positive monocytes, macrophages, and mast cells were present in GO orbital tissue. PDGF-BB stimulated proliferation and hyaluronan and IL-6 production by orbital fibroblasts the most, followed by PDGF-AB and PDGF-AA. Finally, in particular imatinib mesylate and PDGF-BB-neutralizing antibodies reduced IL-6 and hyaluronan production by whole orbital tissue cultures from GO patients. CONCLUSIONS: In GO, mast cells, monocytes, and macrophages may activate orbital fibroblasts via secretion of especially PDGF-AB and PDGF-BB. Preclinical studies with whole orbital tissue cultures show that blocking PDGF-B chain containing isoforms can be a promising treatment for GO.
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Ojo/metabolismo , Oftalmopatía de Graves/metabolismo , Macrófagos/metabolismo , Mastocitos/metabolismo , Monocitos/metabolismo , Factor de Crecimiento Derivado de Plaquetas/biosíntesis , Benzamidas , Proliferación Celular/efectos de los fármacos , Ojo/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Oftalmopatía de Graves/tratamiento farmacológico , Humanos , Ácido Hialurónico/biosíntesis , Mesilato de Imatinib , Interleucina-6/biosíntesis , Macrófagos/efectos de los fármacos , Mastocitos/efectos de los fármacos , Monocitos/efectos de los fármacos , Piperazinas/farmacología , Piperazinas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/farmacología , Pirimidinas/uso terapéuticoRESUMEN
AIM: To describe the effect of additional treatment with anti-TNF-alpha therapy in a case series of 13 patients with serious sight threatening uveitis. METHODS: 13 patients with serious sight threatening uveitis were included, of whom six had Behçet's disease, five had idiopathic posterior uveitis, one had sarcoidosis, and one birdshot retinochoroiditis. Onset and course of ocular inflammation, inflammatory signs, and visual acuity were assessed. Patients were treated with 200 mg (approximately 3 mg/kg) infliximab infusion. Repeat infusions were given based on clinical response. RESULTS: Infliximab treatment resulted in an effective suppression of ocular inflammation in all patients. In patients with non-Behcet's disease uveitis visual acuity in six out of eight improved or was stable. In patients with Behcet's disease visual acuity in five out of six improved or was stable. CONCLUSION: Anti-TNF-alpha treatment may be of value in the treatment of uveitis, and in patients with Behçet's disease, leading to suppression of ocular inflammation, vasculitis, and improvement of vision in the majority. Based on these results a controlled masked study is warranted.
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Anticuerpos Monoclonales/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Uveítis/tratamiento farmacológico , Adulto , Anciano , Síndrome de Behçet/tratamiento farmacológico , Síndrome de Behçet/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Infliximab , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Uveítis/fisiopatología , Uveítis Posterior/tratamiento farmacológico , Uveítis Posterior/fisiopatología , Agudeza Visual/efectos de los fármacosRESUMEN
Somatostatin and its derivatives have been predominantly studied and succesfully used in endocrinological diseases. This article reviews the rationale of the use of somatostatin and its derivatives in ophthalmology based on current understanding of its action in the eye and summarizes previously published controlled studies and case series. The article points out future possible applications. Larger randomised controlled studies are necessary to confirm its current and future use. New ways of application could facilitate its broader use in ophthalmology.
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Oftalmopatías/tratamiento farmacológico , Oftalmología , Somatostatina/análogos & derivados , Somatostatina/uso terapéutico , Inhibidores de la Angiogénesis , Antiinflamatorios , División Celular , Ojo/irrigación sanguínea , Ojo/química , Oftalmopatías/patología , Oftalmopatías/fisiopatología , Humanos , Receptores de Somatostatina/análisis , Receptores de Somatostatina/fisiología , Enfermedades de la Retina/tratamiento farmacológicoRESUMEN
Treatment with cyclosporine (CsA) has considerably improved the visual prognosis of patients suffering from endogenous posterior uveitis (EPU). However, the therapeutic benefits of CsA are partially outweighed by its many side effects, most notably nephrotoxicity and hypertension. Low-dose CsA regimens have reduced toxicity but have not been able to completely eliminate this problem. New therapeutic approaches, such as anti-tumor necrosis factor alpha treatment or immunosuppression with drugs including tacrolimus, sirolimus, and interleukin-2 receptor antibodies, are currently under evaluation. Hopefully such strategies will further reduce the morbidity of EPU and minimize the adverse effects associated with conventional therapies.
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Ciclosporina/uso terapéutico , Uveítis Posterior/tratamiento farmacológico , Ciclosporina/efectos adversos , Interacciones Farmacológicas , Humanos , Hipertensión/inducido químicamente , Inmunosupresores/uso terapéutico , Riñón/efectos de los fármacos , Riñón/patologíaRESUMEN
Diabetic retinopathy is a leading cause of legal blindness in the adult population (30-70 year olds). The anatomical changes that occur in the retina during the course of disease are well defined in the literature but the causes are not yet fully understood. Laser photocoagulation of the retina and vitrectomy are currently used to treat diabetic retinopathy but the procedures are invasive and provide only temporary protection. The use of long-acting analogues of the naturally occurring peptide, somatostatin, has been considered by some a promising therapeutic option for retinopathy over the last decade. Experimental evidence supports its use in diabetic retinopathy but further clinical evidence, from larger treatment groups of longer trial duration, is required. Improved analogues with increased selectivity and modified bi-specific analogues are currently emerging and may help to make the use of somatostatin analogues a more realistic option in the treatment of diabetic retinopathy.
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Retinopatía Diabética/tratamiento farmacológico , Octreótido/uso terapéutico , Somatostatina/análogos & derivados , Animales , Humanos , Resultado del TratamientoRESUMEN
AIM: To evaluate the possibility of translocating autologous peripheral retinal pigment epithelial (RPE) cells and enhance their adhesion to improve functional outcome after choroidal neovascular membrane extraction in patients with subfoveal neovascular membranes. METHODS: A prospective, non-controlled surgical study in eight consecutive patients operated between February and July 2001 with final data monitoring in July 2002. All patients had mixed subfoveal membranes of 2-4 disc diameters. Functional tests included Snellen vision and central fixation testing. During vitrectomy, after the extraction of the neovascular complex, 8 x 10(4)-16 x 10(4) RPE cells were removed from the periphery and translocated under the macula following the submacular injection of 2 microg of poly-L-lysine to promote adhesion of the cells. RESULTS: With a follow up ranging from 3 months to 16 months, a pigmented area was seen in the extraction bed of the neovascular membrane in only one patient. Fixation was at the edge of the extraction bed in three patients. Vision remained the same in five patients and deteriorated in three (all with retinal detachment). Retinal detachment due to proliferative vitreoretinopathy occurred in three patients. CONCLUSIONS: The translocation of autologous peripheral RPE cells after membrane extraction was technically possible in a sterile manner, but was associated with a high proliferative vitreoretinopathy rate and in the present series had no measurable positive effect on functional outcome.
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Neovascularización Coroidal/cirugía , Epitelio Pigmentado Ocular/trasplante , Adulto , Anciano , Anciano de 80 o más Años , Adhesión Celular , Trasplante de Células/efectos adversos , Trasplante de Células/métodos , Neovascularización Coroidal/etiología , Neovascularización Coroidal/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Degeneración Macular/complicaciones , Degeneración Macular/cirugía , Masculino , Epitelio Pigmentado Ocular/patología , Estudios Prospectivos , Resultado del Tratamiento , Agudeza Visual , VitrectomíaRESUMEN
Cancer-associated retinopathy (CAR) is a paraneoplastic syndrome that is characterized by degeneration of the retina as a remote effect of cancer outside the eye. The detection of autoantibodies associated with the retinopathy may precede the diagnosis of the underlying cancer. We have examined the sera of two patients with CAR by Western blot analysis. Autoantibodies to a 40kD antigen doublet and a 35 kD antigen were detected. Tissue specificity of the autoantigens was determined by testing several different tissues. The 40 kD antigen doublet was most abundant in retinal extract but was also present in lung and spleen extracts. The 35 kD antigen showed little tissue specificity and was present in all tissues tested. Fractionation of retinal proteins into water-soluble and -insoluble proteins revealed that the 40 kD antigen doublet was highly insoluble and probably represented membrane-associated proteins. Immunohistochemical analysis of the retina showed that the 40 kD antigens locate to the photoreceptors while the 35 kD antigen is located in the outer plexiform layer.
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Antígenos de Superficie/inmunología , Autoanticuerpos/inmunología , Autoantígenos/inmunología , Proteínas del Ojo/inmunología , Proteínas de la Membrana/inmunología , Nervio Óptico/inmunología , Síndromes Paraneoplásicos/inmunología , Segmento Externo de la Célula en Bastón/inmunología , Adenocarcinoma/complicaciones , Adenocarcinoma/inmunología , Adenocarcinoma/patología , Anciano , Animales , Antígenos de Superficie/análisis , Autoanticuerpos/sangre , Autoantígenos/análisis , Neoplasias del Colon/complicaciones , Neoplasias del Colon/inmunología , Neoplasias del Colon/patología , Defectos de la Visión Cromática/etiología , Defectos de la Visión Cromática/inmunología , Adaptación a la Oscuridad/inmunología , Proteínas del Ojo/análisis , Femenino , Humanos , Masculino , Proteínas de la Membrana/análisis , Síndromes Paraneoplásicos/sangre , Síndromes Paraneoplásicos/patología , Neoplasias de la Próstata/complicaciones , Neoplasias de la Próstata/inmunología , Neoplasias de la Próstata/patología , Ratas , Ratas Wistar , Retina/inmunología , Degeneración Retiniana/etiología , Degeneración Retiniana/inmunología , Solubilidad , Distribución Tisular , Extractos de Tejidos/inmunologíaRESUMEN
PURPOSE: Fas-ligand expression on retinal pigment epithelium is hypothesized to have an inhibitory effect on human ocular neovascularization. METHODS: We studied Fas-ligand expression in the aging retinal pigment epithelium and in early and late stages of age-related maculopathy. Immunohistochemistry with antibodies against Fas-ligand was performed on paraffin-embedded sections of 23 human eye bank eyes (aged 45 to 96 years) and 12 eyes with exudative age-related maculopathy. RESULTS: Fas-ligand expression in retinal pigment epithelium was not related to age or to the presence of early age-related maculopathy. Furthermore, Fas-ligand expression in retinal pigment epithelium was similar in subretinal and subretinal pigment epithelium choroidal neovascular membranes. CONCLUSION: It appears to be unlikely that Fas-ligand expressed on retinal pigment epithelium controls the extension of choroidal neovascular membranes from subretinal pigment epithelium to subretinal.
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Neovascularización Coroidal/metabolismo , Degeneración Macular/metabolismo , Glicoproteínas de Membrana/fisiología , Epitelio Pigmentado Ocular/metabolismo , Anciano , Anciano de 80 o más Años , Envejecimiento/metabolismo , Proteína Ligando Fas , Humanos , Técnicas para Inmunoenzimas , Persona de Mediana Edad , Receptor fas/metabolismoRESUMEN
BACKGROUND: Radiotherapy has recently been employed to treat patients with exudative macular degeneration in order to prevent severe visual loss. Radiotherapy affects the evolution of exudative macular degeneration directly by endothelial toxicity, leading to capillary closure, and/or indirectly through its attenuating effects on the inflammatory response, mediated by macrophages and other inflammatory cells. METHODS: In this study we describe the histopathologic findings in a patient with exudative age-related macular degeneration (AMD) in both eyes whose right eye was treated with radiotherapy (5 times 2 Gy) 3 years before he died. The eyes were enucleated post mortem and investigated by light microscopy. Additionally, immunohistochemical investigation with antibodies against CD34 and CD68 was performed to identify patent endothelial cells and macrophages. RESULTS: Both eyes showed neovascular AMD consisting of mixed fibrocellular and fibrovascular membranes. Capillaries in both the choriocapillaris and the neovascular membrane were patent in both eyes. Macrophages were present in the choroidal neovascularization of both eyes. Neither preexistent choroidal, intraretinal, nor neovascular vessels showed increased wall thickness as sign of radiation damage. CONCLUSION: No radiation-related histopathologic effect could be demonstrated 3 years after radiation therapy in this patient with AMD.
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Degeneración Macular/patología , Degeneración Macular/radioterapia , Anciano , Antígenos CD/metabolismo , Antígenos CD34/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Coroides/irrigación sanguínea , Neovascularización Coroidal/patología , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Exudados y Transudados , Humanos , Técnicas para Inmunoenzimas , Macrófagos/metabolismo , Macrófagos/patología , Masculino , Radiometría , Vasos Retinianos/patologíaRESUMEN
BACKGROUND: It has become increasingly clear that apoptosis is a main event in photoreceptor cell death in a variety of retinal degenerations. We investigated the role of apoptosis in the physiologically aging primate macula. METHODS: Twenty maculae of rhesus monkeys, aged 6-34 years, were investigated. Apoptosis was determined in formalin-fixed, paraffin-embedded eyes using the TUNEL (TdT-mediated dUTP-biotin nick end labeling) method and quantitatively analyzed. Morphology of TUNEL-positive cells was studied by confocal laser microscopy and transmission electron microscopy. The thickness of the outer nuclear layer (ONL) was determined by image analysis. Furthermore, expression of apoptosis-regulating proteins Bcl-x, Fas and Fas Ligand was studied by immunohistochemistry. RESULTS: TUNEL-positive nuclei showed apoptotic features on confocal laser microscopy. They were scattered and sparsely found in the macula, most frequently in the ONL. The thickness of the ONL decreased with increasing age. Apoptosis was found equally distributed at all ages, although in the two oldest maculae up to 13 times more apoptosis was found. Expression of Bcl-x, Fas and Fas Ligand was equal at all ages. CONCLUSION: Our findings indicate that apoptosis in the primate macula occurs at all ages at similar rates, possibly increasing in the oldest age group, and may account for the decreasing thickness of the primate macula with age.
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Apoptosis , Mácula Lútea/patología , Envejecimiento/metabolismo , Animales , Biomarcadores , Proteína Ligando Fas , Etiquetado Corte-Fin in Situ , Macaca mulatta , Mácula Lútea/metabolismo , Glicoproteínas de Membrana/metabolismo , Microscopía Confocal , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteína bcl-X , Receptor fas/metabolismoRESUMEN
PURPOSE: The growth of ocular neovascularization is regulated by a balance between stimulating and inhibiting growth factors. Somatostatin affects angiogenesis by inhibiting the growth hormone-insulin-like growth factor axis and also has a direct antiproliferative effect on human retinal endothelial cells. The purpose of our study is to investigate the expression of somatostatin receptor (sst) subtypes and particularly sst subtype 2A (sst2A) in normal human macula, and to study sst2A in different stages of age-related maculopathy (ARM), because of the potential anti-angiogenic effect of somatostatin analogues. METHODS: Sixteen eyes (10 enucleated eyes, 4 donor eyes, and 2 surgically removed choroidal neovascular [CNV] membranes) of 15 patients with eyes at different stages of ARM were used for immunohistochemistry. Formaldehyde-fixed paraffin-embedded slides were incubated with a polyclonal anti-human sst2A antibody. mRNA expression of five ssts and somatostatin was determined in the posterior pole of three normal human eyes by reverse transcriptase-polymerase chain reaction. RESULTS: The immunohistochemical expression of sstA in newly formed endothelial cells and fibroblast-like cells was strong in fibrovascular CNV membranes. mRNA of sst subtypes 1, 2A, and 3, as well as somatostatin, was present in the normal posterior pole; sst subtypes 4 and 5 were not detectable. CONCLUSIONS: Most early-formed CNV in ARM express sst2A. The presence of mRNA of sst subtype 2A was observed in normal human macula, and subtypes 1 and 3 and somatostatin are also present. sst2A receptors bind potential anti-angiogenic somatostatin analogues such as octreotide. Therefore, somatostatin analogues may be an effective therapy in early stages of CNV in ARM.
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Neovascularización Coroidal/genética , Degeneración Macular/complicaciones , ARN Mensajero/biosíntesis , Receptores de Somatostatina/genética , Adulto , Anciano , Anciano de 80 o más Años , Neovascularización Coroidal/etiología , Neovascularización Coroidal/metabolismo , Cartilla de ADN/química , Femenino , Expresión Génica , Humanos , Técnicas para Inmunoenzimas , Mácula Lútea/metabolismo , Masculino , Persona de Mediana Edad , Receptores de Somatostatina/biosíntesis , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
BACKGROUND/AIMS: Earlier studies on intraocular tissue have demonstrated that T lymphocytes play a major role in the pathogenesis of uveitis. Adhesion molecules are immunoregulatory molecules for the interaction between T lymphocytes and vascular endothelium and they play an important role in the recruitment of specific T lymphocytes from the circulation into inflamed tissue. In uveitis an increased expression of some of these adhesion molecules may be expected. METHODS: The presence of adhesion molecules was investigated in iris biopsy specimens from 11 patients with uveitis and eight controls (patients with primary open angle glaucoma) immunohistochemically with a panel of monoclonal antibodies: LECAM (CD 62L), ICAM-1 (CD 54), LFA-1 (CD 11a/18), VCAM-1 (CD 106), VLA-4 (CD 49d), and HECA-452, a marker for high endothelial venules. RESULTS: Positive staining for ICAM-1, LFA-1 and VCAM-1 was found in the iris in a significantly higher number of uveitis patients than in controls. The remaining adhesion molecules were also found in a higher number of uveitis patients than in controls, but this difference did not reach statistical significance. CONCLUSION: An increased expression of adhesion molecules was found in the iris of patients with uveitis, indicating an immunoregulatory function for adhesion molecules in the pathogenesis of uveitis.
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Moléculas de Adhesión Celular/análisis , Iris/química , Uveítis/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Glaucoma de Ángulo Abierto/metabolismo , Humanos , Inmunohistoquímica , Molécula 1 de Adhesión Intercelular/análisis , Antígeno-1 Asociado a Función de Linfocito/análisis , Masculino , Persona de Mediana Edad , Uveítis/inmunología , Uveítis/patología , Molécula 1 de Adhesión Celular Vascular/análisisAsunto(s)
Edema Macular/tratamiento farmacológico , Octreótido/uso terapéutico , Adulto , Humanos , MasculinoRESUMEN
We report a family with a neonate who was severely damaged by intracranial haemorrhages. These probably occurred before the 20th week of gestation. The neonate had a moderate thrombocytopenia. In the maternal serum anti-HPA-1b and anti-HPA-2a alloantibodies were detected. Third-generation assays were applied to identify the alloantibodies. No other cause for the bleeding was found. Probably the combination of anti-HPA-1b and anti-HPA-2a alloantibodies, directed against the platelet fibrinogen receptor and the von Willebrand receptor, respectively, induced a thrombocytopenia and a thrombocytopathy.
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Antígenos de Plaqueta Humana/inmunología , Encéfalo/anomalías , Hemorragia Cerebral/etiología , Transfusión Fetomaterna/inmunología , Isoanticuerpos/análisis , Trombocitopenia/congénito , Plaquetas/inmunología , Hemorragia Cerebral/congénito , Hemorragia Cerebral/inmunología , Femenino , Enfermedades Fetales/etiología , Humanos , Recién Nacido , Glicoproteínas de Membrana Plaquetaria/inmunología , Embarazo , Receptores de Superficie Celular/inmunología , Trombocitopenia/inmunologíaRESUMEN
The serum of a Caucasian woman who gave birth to a child with neonatal alloimmune thrombocytopenia contained antibodies directed against a platelet antigen of the newborn. There was no incompatibility for the known platelet alloantigens HPA-1 to HPA-7 or for the private or low-frequency antigens Sra and Vaa, between the platelets of the parents. However, crossmatching with the serum of the mother and the platelets of the child and the father was strongly positive, suggesting a new platelet antibody specificity. To investigate the inheritance of the 'Groa' antigen involved, the available family members were tested in the platelet immunofluorescence test (PIFT) and the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay. The Groa antigen was found to be inherited in an autosomal-codominant fashion. In the MAIPA, we localized the Groa antigen on the glycoprotein IIb/IIIa complex (alpha IIb beta 3). The GP IIb/IIIa localization was confirmed in immunoprecipitation studies. In Western blotting experiments, we further localized the Groa antigen on the GP IIIa (beta 3) subunit of the GP IIb/IIIa complex. Until now we have tested approximately 400 unrelated donors. None of these appeared to be positive for the Groa antigen, suggesting a phenotype frequency in the Dutch population of less than 0.01.