ABSTRACT
Resumen Los autoanticuerpos anticitocinas (ACAA) han sido reportados como causa importante de inmunodeficiencias secundarias. Altos títulos de autoanticuerpos neutralizantes pueden causar susceptibilidad a diferentes enfermedades infecciosas potencialmente mortales. Por ejemplo, se ha informado que autoanticuerpos neutralizantes contra IFNγ se correlacionan con susceptibilidad a infecciones micobacterianas y patógenos fúngicos intracelulares. Autoanticuerpos contra IL-6 se detectaron en pacientes con abscesos subcutáneos y celulitis estafilocócica recurrente; asimismo, pacientes con criptococosis, nocardiosis y proteinosis alveolar pulmonar fueron positivos a autoanticuerpos contra GM-CSF. También se ha establecido una relación entre los autoanticuerpos contra IL-17 e IL-22 y las infecciones crónicas por Candida en mucosas, que se han identificado en pacientes con poliendocrinopatía autoinmune tipo 1 o timoma. Recientemente se han reportado autoanticuerpos contra interferón tipo I durante el inicio de COVID-19 aguda. Estos ACAA se asemejan a defectos genéticos en citocinas o en sus rutas de señalización. Por ello, pueden considerarse fenocopias de inmunodeficiencias primarias. De esta forma, la detección de ACAA podría ser importante en el diagnóstico, particularmente en pacientes con enfermedades de aparición tardía, para decidir los tratamientos apropiados. Esta revisión presenta una descripción general de la comprensión actual de las inmunodeficiencias secundarias asociadas a ACAA.
Abstract Anti-cytokine autoantibodies (ACAA) have been reported to be an important cause of secondary immunodeficiencies. High titers of neutralizing autoantibodies may cause susceptibility to different life-threatening infectious diseases. For example, neutralizing autoantibodies against IFNγ have been reported to be correlated with susceptibility to mycobacterial infections and intracellular fungal pathogens. Autoantibodies against IL-6 were detected in patients with subcutaneous abscesses and recurrent staphylococcal cellulitis; on the other hand, patients with cryptococcosis, nocardiosis, and pulmonary alveolar proteinosis were positive for autoantibodies to GM-CSF. A relationship has also been established between autoantibodies against IL-17 and IL-22 and chronic mucosal Candida infections, which have been identified in patients with APECED or thymoma. Autoantibodies against type-I IFN have been recently reported during the onset of acute COVID-19. These ACAAs resemble genetic defects in cytokines or their signaling pathways. Therefore, they may be considered to be primary immunodeficiencies phenocopies. Consequently, the detection of ACAA could be important in the diagnosis of patients, particularly in the case of late-onset diseases, in order to decide appropriate treatments. This review presents an overview of current understanding of ACAA-associated secondary immunodeficiencies.
ABSTRACT
Resumen Las inmunodeficiencias humorales (IDH) comprenden un grupo de enfermedades caracterizadas por una deficiente respuesta mediada por anticuerpos. Se clasifican en primarias (IDHP), causa das por defectos propios del sistema inmune, o secundarias (IDHS) a otras enfermedades o fármacos. Nuestro objetivo fue revisar la evolución de las IDH asistidas en la Unidad Inmunología del Hospital Durand entre 1982 y 2020, dividido en dos periodos, Periodo I (1982-2009) y Periodo II (2010-2020); para evaluar el crecimiento de éstas, sus características epidemiológicas y las formas de tratamiento. Se evaluaron 205 pacientes, 176 (85.8%) IDHP y 29 (14.2%) IDHS. Las IDHP más diagnosticadas fueron: inmunodeficiencia común variable en 104 (59%) pacientes, agammaglobulinemia ligada al cromosoma X en 17 (9.6%) y deficiencia selectiva de IgA en 26 (14.8%). En 25 (14.2%) IDHP se realizó un diagnóstico molecular. Las causas de IDHS fueron: secundaria a rituximab en 21 (72.4%) pacientes, enfermedades hematológicas en tres (10.2%) y fármacos antiepilépticos en tres. Un total de 161 (78.5%) pacientes recibieron gammaglobulina, 140 (87%) IDHP y 21 (13%) IDHS; 152 (94.4%) fueron tratados con gammaglobulina endovenosa y nueve (5.6%) con gammaglobulina subcutánea. De los tratados inicialmente con forma endovenosa, 30 (19.7%) cambiaron a subcutánea. El crecimiento en la can tidad de pacientes entre ambos periodos del estudio fue mayor al 250%, y al 700% en pacientes incorporados por año. El crecimiento de las IDHS con relación al de las IDHP fue más del doble. Al finalizar el estudio 125 pacientes continuaban en seguimiento, 80% IDHP y 20% IDHS, y 14 fallecieron.
Abstract Antibody deficiencies (AD) are characterized by low or absent immunoglobulin levels or the inability to develop a specific antibody response. They are classified in primary (PAD) when there is an intrinsic immune defect, or secondary (SAD) to other dis eases or drugs. The aim of our study was to review the evolutio n of AD assisted at the Immunology Unit, Hospital Durand between 1982 and 2020, divided into two periods: Period I (1982-2009) and Period II (2010-2020); to evaluate their growth, epidemiologic features and treatment options. A total of 205 patients were identified, 176 (85.8%) with PAD and 29 (14.2%) with SAD. The most frequent PAD were common variable immunodeficiency in 104 (59%) patients, X linked agammaglobulinemia in 17 (9.6%) and selective IgA deficiency in 26 (14.8%). Genetic defects were found in 25 (14.2%) patients with PAD. SAD cases were associated with rituximab in 21 (72.4%) subjects, haematological disease in three (10.2%) and with antiepileptic drugs in other three; 161 (78.5%) patients were treated with immunoglobulins, 140 (87%) PAD y 21 (13%) SAD; 152 (94.4%) received intravenous immunoglobulins and nine (5.6%) subcutaneous immunoglobulins. Thirty (19.7%) patients treated at first with intravenous immunoglobulins changed to subcutaneous formulations. The increase in number of patients between both periods was greater than 250%, and more than 700% in patients added per year. SAD growth was greater than twice times comparing with PAD. By the end of the study 125 patients continued in follow up, 80% PAD y 20% SAD and 14 died.
ABSTRACT
Resumen La enfermedad COVID-19, causada por el virus SARS-CoV-2, surgió a fines de 2019 en Wuhan, China. La evolución clínica es variable, así como la tasa de mortalidad, que es mayor en pacientes mayores de 65 años y en quienes padecen enfermedades subyacentes. Las inmunodeficiencias son potenciales factores de riesgo para formas graves de COVID-19. Los pacientes con inmunodeficiencias tienen además mayor frecuencia de complicaciones no infecciosas, que podrían representar un riesgo adicional. Hasta el momento existen escasas publicaciones sobre asociación COVID-19 e inmunodeficiencias humorales. Considerando la importancia del estudio de esta nueva enfermedad viral y de su potencial repercusión en la salud de los pacien tes con inmunodeficiencias presentamos seis casos de COVID-19 en adultos con déficit de anticuerpos (tres mujeres y tres varones, edad promedio 48.5 años, rango 20-67). Cuatro tenían inmunodeficiencias primarias: inmunodeficiencia común variable (n: 3) y agammaglobulinemia ligada al cromosoma X (n: 1). Los otro dos tenían hipogammaglobulinemia secundaria, en un caso asociada a timoma (síndrome de Good), y en el otro a tratamiento con rituximab. La evolución fue favorable en todos menos en el paciente con síndrome de Good, quien presentaba un marcado deterioro del estado general antes de contraer COVID-19.
Abstract COVID-19, caused by SARS-CoV-2, emerged in late 2019 in Wuhan, China. Its clinical course is variable, as well as the mortality rate, which is higher among people over 65 years of age and persons with underlying conditions. Immunodeficiencies are po tential risk factors for severe forms of COVID-19. Furthermore, patients with immunodeficiencies often undergo non-infectious complications, which could bear additional risk. So far, few reports of patients with COVID-19 and humoral immunodeficiencies have been published. Considering the importance of the study of this new viral disease and its potential health impact on patients with immunodeficiency disorders, we present six cases of COVID-19 in patients with impaired humoral immunity. Three were women and three were men. The average age was 48.5 years (range 20-67). Four had been diagnosed with primary antibody deficiency: three had common variable immunodeficiency and one had X-linked agammaglobulinemia. The other two patients had secondary hypogammaglobulinemia, one was associated with thymoma (Good's syndrome), and the other was associated with rituximab treatment. The evolution was favorable in all except the patient with Good's syndrome, who pre sented a marked decline in clinical status before contracting COVID-19.
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Young Adult , Thymoma , Thymus Neoplasms , Agammaglobulinemia , Primary Immunodeficiency Diseases , COVID-19 , SARS-CoV-2ABSTRACT
Objective To understand the clinical characteristics of staphylococcal bloodstream infection in patients with secondary immunodeficiency,as well as the distribution and drug resistance of Staphylococcus aureus (SAU)and coagulase negative Staphylococcus (CNS).Methods A total of 101 patients with Staphylococcus isolated from blood sample were retrospectively reviewed in our hospital.The patients were classified into a group with secondary immunodeficiency and another group with normal immune function as control group.SPSS 18.0 statistical software was used to analyze the data,and compare the two groups of patients in terms of clinical characteristics,pathogens,antibiotic resistance,etc.Results All the 70 patients with staphylococcal bloodstream infection and secondary immunodeficiency had various degrees of fever except 2 cases (temperature < 36 ℃).Chills and shiver were reported in 30.0% of the patients,and migratory lesions in 15.5% of the patients.Lungs were the most common site of infection.About 11.4% of the patients complicated with septic shock.The case strains of SAU,of which 18 (43.9%)strains were MRSA,CNS 29 (41.4%)strains,of which 24 (82.8%)strains were MRCNS.In the control group,26 (83.9%)strains of SAU were identified,of which 11 (42.3%)strains were MRSA,and all the 5 (16.1%)strains of CNS were identified as MRCNS.The incidence of CNS infection in the patients with secondary immunodeficiency was significantly different from that in the control group (P =0.013).All the MRS strains were multidrug-resistant organism (MDRO)except one strain of Staphylococcus intermedius .The staphylococcal strains isolated from the patients with secondary immunodeficiency showed high rate of resistance to penicillin (100%), clindamycin (73.0%), erythromycin (90.0%)and gentamycin (61.0%).No strain was found resistant to tigecycline,linezolid or vancomycin.The resistance rate did not show significant difference between the patients with or without secondary immunodeficiency. Conclusions The clinical characteristics of staphylococcal bloodstream infection in the patients with secondary immunodeficiency are similar to the patients without secondary immunodeficiency,except higher incidence of septic shock and death,but the incidence of CNS infection is relatively higher,MDRO is more prevalent.Antimicrobial agents should be prescribed in clinical practice according to disease conditions and the result of antimicrobial susceptibility testing.