Genetic association of IFN-γ +874T/A polymorphism in Mexican patients with drug-induced Stevens-Johnson syndrome/toxic epidermal necrolysis.

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are rare, but potentially life-threatening diseases, characterized by widespread epidermal necrosis and are predominantly drug induced. There is a paucity of data regarding the role of cytokine and cytokine receptors polymorphisms in the pathoimmunology of SJS/TEN. The aim of this study was to investigate the role of TNF-α-308, IFN-γ +874, IL-10-1082, IL-13 Arg130Gln, and IL-4R Gln551Arg gene polymorphisms in SJS/TEN in Mexican Mestizo patients. Twenty-nine unrelated SJS/TEN patients and 128 unrelated healthy individuals were studied. Genomic extraction was carried out from complete blood samples using the salting out method. The PCR-RFLP method was used to amplify the following polymorphisms: TNF-α-308, IFN-γ +874, IL-10-1082, IL-13 Arg130Gln, and IL-4R Gln551Arg. TNF-α-308, IL-10-1082, IL-13 Arg130Gln, and IL-4R Gln551Arg polymorphisms were not associated with the genetic susceptibility to SJS/TEN. The distribution of TT, TA, AA genotypes of IFN-γ +874 was significantly different in SJS/TEN patients compared with controls (pC = 0.012). TA and AA genotypes were grouped to highlight the differences between patients and controls given by the absence of the AA genotype in the group of patients (pC = 0.03, OR = 3.61 95 % CI 1.20-11.6). This preliminary study suggests that IFN-γ +874 T/A polymorphism is associated with SJS/TEN.

Peripheral regulatory cells immunophenotyping in kidney transplant recipients with different clinical profiles: a cross-sectional study.

Regulatory Foxp3-expressing T cells (Tregs), IL-10-producing B cells (Bregs), and IDO-expressing dendritic cells (DCregs) downregulate inflammatory processes and induces peripheral tolerance. These subpopulations also might participate in maintaining allograft immunological quiescence in kidney transplant recipients (KTRs) with an excellent long-term graft function under immunosuppression (ELTGF). The aim of the study was to characterize and to enumerate peripheral Tregs, Bregs, and DCregs in KTR with an ELTGF for more than 5 years after transplant. Fourteen KTR with an ELTGF, 9 KTR with chronic graft dysfunction (CGD), and 12 healthy donors (HDs) were included in the study. CD19(+)-expressing peripheral B lymphocytes were purified by positive selection. IL-10-producing B cells, CD4(+)/CD25(hi), and CD8(+)/CD28(-) Tregs, as well as CCR6(+)/CD123(+)/IDO(+) DCs, were quantitated by flow cytometry. IL-10-producing Bregs (immature/transitional, but not CD19(+)/CD38(hi)/CD24(hi)/CD27(+)B10 cells), CCR6(+)/CD123(+)/IDO(+) DCs, and Tregs from ELTGF patients had similar or higher percentages versus HD (P < 0.05). By contrast, number of Tregs, DCregs, and Bregs except for CD27(+)B10 cells from CGD patients had lower levels versus HD and ELTGF patients (P < 0.05). The findings of this exploratory study might suggest that in ELTGF patients, peripheral tolerance mechanisms could be directly involved in the maintenance of a quiescent immunologic state and graft function stability.

Genetic association of CCR5 promoter single nucleotide polymorphism in seronegative and seropositive rheumatoid arthritis.

The aim of this study was to investigate the possible role of the CCR5 59029 A→G promoter point mutation polymorphism in determining the susceptibility to rheumatoid factor-positive and rheumatoid factor-negative rheumatoid arthritis. This polymorphism was assessed in 85 seropositive and 39 seronegative rheumatoid arthritis patients and in 126 healthy individuals of the same geographic and ethnic origin. We found an increase in the genetic frequency of the A allele in the 59029 A→G promoter region of the CCR5 receptor in patients with rheumatoid arthritis compared with healthy controls (p = 0.01; OR = 1.5, 95% CI (1.0-2.2). Likewise, the homozygous state for the A allele was found to be more frequent in rheumatoid arthritis patients, again when compared with healthy controls (p = 0.03; OR = 1.8, 95% CI 1.0-3.0). The increased frequency of the A allele was more evident in the more benign, seronegative rheumatoid arthritis group when compared with controls (p = 0.003; OR 2.4 95% CI 1.3-4.4), and when combining the A homozygous and the AG heterozygous patients compared with healthy subjects. These results suggest that this CCR5 promoter polymorphism seems to play an important role in determining different clinical courses in both forms of rheumatoid arthritis.

Cincuentenario del descubrimiento de la estructura química de los anticuerpos / Fiftieth anniversary of the description of the chemical structure of antibodies

La identificación de la propiedad antitóxica del suero en 1890 por Emil von Behring y la introducción del término “Antikörper” por Paul Ehrlich en 1891 para referirse a uno de los mecanismos de defensa más relevantes del sistema inmunitario adaptativo, es decir, los mediadores de la respuesta inmunitaria humoral, marcan el inicio de la etapa de la inmunología moderna. La estructura en “Y” fue descrita hace cincuenta años por Gerald M. Edelman y Rodney R. Porter. Así, al cumplirse el cincuentenario de la descripción de la estructura química de los anticuerpos, consideramos oportuno no dejar pasar inadvertido el hecho a través de una breve remembranza y la revisión de dichos hallazgos (AU)

The identification of the antitoxic property of serum in 1890 by Emil von Behring and the introduction of the term “Antikörper” by Paul Ehrlich in 1891 referring to one of the most relevant mechanisms of defense of the adaptive immune system, i.e., the humoral immune response mediators, mark the beginning of modern immunology. The “Y” structure was described 50 years ago by Gerald M. Edelman and Rodney R. Porter. Thus, on the fiftieth anniversary of the description of the chemical structure of antibodies, we consider it appropriate to celebrate this fact by sketching a brief outline and review of these epoch-making achievements (AU)

[Coxib: a feasible therapeutic alternative in patients with intolerance or hypersensitivity to acetilsallicilic acid, non-steroidal antiinflammatory drugs and paracetamol]. / Coxib: una alternativa terapéutica factible en pacientes con intoleranciao hipersensibilidad al ácido acetilsalicílico, antiinflamatorios no esteroideos y paracetamol.

Aspirin, non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol are the most frequent drugs used worldwide for the management of pain, inflammation and fever associated with many acute and chronic conditions. Despite of its analgesic, anti-inflammatory and antipyretic properties, all display adverse effects mediated by the same mechanisms by which they control pain, inflammation and fever. A relatively frequent problem with the use of NSAIDs and/or aspirin, and less frequently with paracetamol, is the development of intolerance and hypersensitivity reactions, a situation for which diverse alternatives have been proposed. One of these includes the use of cyclo-oxigenase-2 specific inhibitors (COXIB), a therapeutic modality analyzed in the present paper.

[Fiftieth anniversary of the description of the chemical structure of antibodies]. / Cincuentenario del descubrimiento de la estructura química de los anticuerpos.

The identification of the antitoxic property of serum in 1890 by Emil von Behring and the introduction of the term "Antikörper" by Paul Ehrlich in 1891 referring to one of the most relevant mechanisms of defense of the adaptive immune system, i.e., the humoral immune response mediators, mark the beginning of modern immunology. The "Y" structure was described 50 years ago by Gerald M. Edelman and Rodney R. Porter. Thus, on the fiftieth anniversary of the description of the chemical structure of antibodies, we consider it appropriate to celebrate this fact by sketching a brief outline and review of these epoch-making achievements.

[A review of interferons: fifty years later (1957-2007)]. / Interferón: 50 años después (1957-2007).

Initially identified as a defense mechanism against viral infections, in the last 50 years interferons have been defined a group of substances belonging to the cytokine family indispensable for the normal functioning of the immune system. Derived from their pleiotropic functions interferons were the first biological products used to treat several diseases. Their properties have progressively placed them as the first treatment choice for chronic infection with hepatitis B virus, hepatitis C virus, multiple sclerosis, some forms of leukemia, melanoma, etc. It has been noted however that the administration of supra physiological doses of interferons with therapeutic objectives, independently of its primary indication, has been associated with significant toxicity, including autoimmunity and induction of more than thirty different autoimmune diseases.

Interferón: 50 años después (1957-2007) / A review of interferons: fifty years later (1957-2007)

Identificados inicialmente como un mecanismo de defensa contra las infecciones virales, en el transcurso de los últimos 50 años se ha definido que los interferones forman parte de la extensa familia de las citocinas, sustancias indispensables para el funcionamiento del sistema inmunológico. Debido a sus diversas funciones pleiotrópicas, los interferones fueron las primeras citocinas empleadas para el manejo de una amplia gama de padecimientos, propiedades que progresivamente los han colocado como medicamentos de primera elección para el tratamiento de la infección crónica por el virus de la hepatitis B, virus de la hepatitis C, esclerosis múltiple, algunas leucemias, melanoma, etc. No obstante, la administración de dosis suprafisiológicas de interferones con fines terapéuticos, independientemente de su indicación primaria, se han asociado con toxicidad importante, incluyendo la inducción de autoinmunidad y más de 30 enfermedades autoinmunes diferentes.

Initially identified as a defense mechanism against viral infections, in the last 50 years interferons have been defined a group of substances belonging to the cytokine family indispensable for the normal functioning of the immune system. Derived from their pleiotropic functions interferons were the first biological products used to treat several diseases. Their properties have progressively placed them as the first treatment choice for chronic infection with hepatitis B virus, hepatitis C virus, multiple sclerosis, some forms of leukemia, melanoma, etc. It has been noted however that the administration of supra physiological doses of interferons with therapeutic objectives, independently of its primary indication, has been associated with significant toxicity, including autoimmunity and induction of more than thirty different autoimmune diseases.