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Evaluaci贸n de la presencia de anticuerpos anti prote铆nas/p茅ptidos carbamilados y su asociaci贸n con variables de actividad reumatol贸gica y periodontal en pacientes con ar temprana y familiares en primer grado de consanguinidad
Introducci贸n: La Artritis Reumatoide (AR), es una enfermedad inflamatoria autoinmune caracterizada por destrucci贸n del cart铆lago y hueso adem谩s de producci贸n de autoanticuerpos. La AR est谩 asociada a modificaciones postraduccionales como la carbamilaci贸n, proceso que induce la formaci贸n de autoanticuerpos dirigidos a diferentes prote铆nas. Estos anticuerpos se asocian a severidad y progresi贸n de la enfermedad y se han observado antes de la aparici贸n de los s铆ntomas cl铆nicos, por esto la importancia de estudiar estadios tempranos de AR (ART) y familiares consangu铆neos (FDR). Se conoce que hay diferencia en la presencia de anticuerpos anti prote铆nas/p茅ptidos carbamilados entre ART y controles sanos, pero no entre FDR comparado con controles por lo que este trabajo explora cu谩l es la asociaci贸n entre la presencia de anticuerpos anti prote铆nas/p茅ptidos carbamilados con variables reumatol贸gicas en estos individuos. Metodolog铆a: Los anticuerpos anti fibrin贸geno carbamilado (anti-FCS-Carp) y anti p茅ptidos de fibrin贸geno carbamilados (anti-Ca-Fib2 y anti-Ca-Fib3) en pacientes con ART y FDR pareados con controles fueron medidos por ELISA. Las asociaciones se analizaron por Chi cuadrado y test exacto de Fisher. Las comparaciones por prueba de McNemar y se realiz贸 una regresi贸n log铆stica condicional ajustando posibles variables de confusi贸n (edad y consumo de cigarrillo) para establecer la asociaci贸n entre anti-FSC-Carp o anti-Fib-Carp y la condici贸n de AR y FDR. Resultados: Se observ贸 mayor frecuencia en la aparici贸n de anticuerpos anti-CCP en FDR (19.3%) comparado con el grupo CTRL (6.45%), mostr谩ndose una asociaci贸n de riesgo tres veces mayor en este grupo de individuos (OR 3.6 95%IC: 21.44-11.05 p=0.002).As铆 mismo, este grupo de sujetos presentaron mayor n煤mero de articulaciones dolorosas (37.9%) vs CTRL (22.58%) (OR 2.18 95%IC: 1.17-4.23 p=0.007), y mayor n煤mero de articulaciones inflamadas en FDR 15.32% vs 4.03% de los controles, (OR 5.6 95%IC: 1.63- 30.18 p=0.002). en el grupo de ART el EC se encontr贸 en un 52.9% y de estos el 54.9% presentaban al menos un alelo y el 11.8% expresaron dos alelos HLA-DRB1 EC en el grupo FDR La presencia de EC estuvo en el 53.2% y el 45.2% presentaban al menos un alelo y el 8.1% expresaron dos alelos HLA-DRB1 EC . En cuanto a la frecuencia positiva de los anticuerpos anti-FCS-Carp positivo en el grupo de pacientes comparado con el grupo control se encontro una diferencia de 47.1% vs. l7.8%, respectivamente, (OR 7.6 95%IC: 2.3-39.88 p= 0.0001), y en cuanto a la frecuencia positiva de los anticuerpos contra los p茅ptidos carbamilados solo los anti-Ca-Fib2 positivos se encontraron en mayor porcentaje 47,1% pacientes vs 13,7% en CTRL (OR 6.6 95%IC: 1.97- 35.0 p = 0.0005), los anti-FCS-Carp se asociaron con el alelo no EC *1501 (p= 0.033) y con el alelo EC*1402 (p=0.027) , los anticuerpos anti-Ca-Fib2 se asociaron con la presencia de FR positivo (p = 0.022) y con anti-CCP positivo mayor a 60 U (p = 0.032) y con alelos HLA-DRB1 EC *0405 (p= 0.050) y los anti-Ca-Fib3 se asoci贸 con DAS28-VSG (p= 0.046) y con el alelo HLA-DRB1 EC *1402 (p=0.050) . Por otro lado, se observ贸 un mayor porcentaje de los anti-FCS-Carp positivo en el grupo de FDR comparado con de los CTRL 25.00% vs 14.52%, respectivamente (OR 2.625 95%IC: 1.11-6.85 p=0.015). Los anti-Ca-Fib2 positivos estaban presenten un mayor porcentaje 34.68% vs 15.32% FDR respecto a los CTRL, respectivamente (OR 4.0 95%IC: 1.80-10.04 p=0.001)., Los anti-Ca-Fib3 positivos predominaron tambi茅n en un mayor porcentaje en los FDR 33.06% vs 11.29% CTRL (OR 4.85 95%IC: 2.11- 12.98 p=0.001), los anticuerpos anti-FCS-Carp se asociaron con la presencia del alelo EC *1402 (p=0.035) y tambi茅n se encontr贸 asociaci贸n con niveles de PCR (p=0.016) y se correlacion贸 d茅bilmente con FR (r =0.26 p=0.0034) y, con la presencia de articulaciones dolorosas (r = 0.18 p=0.0425)los anti-Ca-Fib2 se asociaron con la presencia del alelo HLA-DRB1 EC *1501 (p=0.03) y los anti-Ca-Fib3 demostraron una asociaci贸n con FR positivo (p= 0.0012) adem谩s se encontr贸 que la condici贸n de FDR se asocia con la presencia de anti-Ca-Fib3 (OR 2.976 95%IC: 1.084-8.166 p=0.034) y con la presencia de articulaciones dolorosas (OR 2.28295%IC: 1.047-4.971 p=0.038) Conclusi贸n: La respuesta humoral en ART puede estar restringida en parte a regiones espec铆ficas de la cadena 尾 de fibrin贸geno carbamilado pudi茅ndose considerar a futuro como otro biomarcador de esta enfermedad en un subgrupo de pacientes. Los autoanticuerpos anti p茅ptidos anti-Ca-Fib3 y anti- Ca-Fib2 pueden ser importantes marcadores en sujetos sanos con riesgo gen茅tico (FDR) debido a la relaci贸n encontrada con manifestaciones inflamatorias articulares que podr铆a sugerirlos potenciales biomarcadores tempranos para el desarrollo de AR.Departamento Administrativo de Ciencia, Tecnolog铆a e Innovaci贸n (Colciencias)Hospital Militar CentralIntroduction: Rheumatoid Arthritis (RA) is an inflammatory autoimmune disease characterized by the destruction of cartilage and bone as well as the production of autoantibodies. RA is associated with post-translational modifications such as carbamylation, a process that induces the formation of autoantibodies directed to different proteins. These were associated with a severity and progression of the disease and have been observed before the onset of clinical symptoms, for example, the importance of studying the temporal stages of RA (ART) and blood relatives (FDR). It is known that there is a difference in the presence of carbamylated protein / peptide antibodies between ART and healthy controls, but not between FDR and controls, so that this work exploits the association between the presence of carbamylated proteins / peptides antibodies with rheumatological variables. in these individuals. Methodology: Antibodies against carbamylated fibrinogen (anti-FCS-Carp) and anti-carbamylated fibrinogen peptides (anti-Ca-Fib2 and anti-Ca-Fib3) in patients with ART and FDR. The associations were analyzed by Chi square and Fisher's test. The comparisons by the McNemar test and a logistic regression of the situation were adjusted to the possible confounding variables (age and cigarette consumption) to establish the association between anti-FSC-Carp or anti-Fib-Carp and the condition of AR and FDR. Results: A higher frequency was observed in the appearance of anti-CCP antibodies in FDR (19.3%) compared to the CTRL group (6.45%), showing a risk association three times higher in this group of individuals (O 3.6 95% CI : 21.44-11.05 p = 0.002) .Similarly, this group of subjects had a greater number of painful joints (37.9%) vs CTRL (22.58%) (OR 2.18 95% CI: 1.17-4.23 p = 0.007), and more Inflamed joints in FDR 15.32% vs 4.03% of controls, (OR 5.6 95% CI: 1.63- 30.18 p = 0.002). in the ART group the EC was found in 52.9% and 54.9% presented in less than one allele and 11.8% expressed two alleles HLA-DRB1 EC in the FDR group The presence of EC was in 53.2% and 45%. , 2% present at least one allele and 8.1% express two HLA-DRB1 EC alleles. Regarding the positive frequency of anti-FCS-positive Carp antibodies in the group of patients compared with the control group, a difference of 47.1% versus 17.8%, respectively, was found (OR 7.6 95% CI: 2.3-39.88 p = 0.0001), and in terms of the positive frequency of the antibodies against the carbamylated peptides, only the results of anti-Ca-Fib2 positive were found in a higher percentage of 47.1% patients vs 13.7% in CTRL (OR 6, 6 95% CI: 1.97-35.0 p = 0.0005), the anti-FCS-Carp was associated with the non-EC allele * 1501 (p = 0.033) and with the EC allele * 1402 (p = 0.027), the anti- Ca-Fib2 was associated with the presence of positive FR (p = 0.022) and with anti-CCP positive greater than 60 U (p = 0.032) and with alleles HLA-DRB1 EC * 0405 (p = 0.050) and anti-Ca Fib3 was associated with DAS28-VSG (p = 0.046) and with the allele HLA-DRB1 EC * 1402 (p = 0.050). On the other hand, a higher percentage of anti-FCS-positive Carp was observed in the FDR group compared to the CTRL 25.00% vs 14.52%, respectively (OR 2.625 95% CI: 1.11-6.85 p = 0.015). The results of anti-Ca-Fib2 positive were present in a higher percentage of 34.68% vs 15.32% FDR with respect to the CTRL, respectively (O 4.0 95% CI: 1.80-10.04 p = 0.001)., The results of anti-Ca -Fib3 also predominated in a higher percentage in the FDR 33.06% vs 11.29% CTRL (OR 4.85 95% CI: 2.11- 12.98 p = 0.001), the anti-FCS-Carp antibodies were associated with the presence of the allele EC * 1402 ( p = 0.035) and it was also associated with CRP levels (p = 0.016) and it was weakly correlated with FR (r = 0.26 p = 0.0034) and, with the presence of painful joints (r = 0.18 p = 0.0425) the anti- Ca-Fib2 was associated with the presence of the allele HLA-DRB1 EC * 1501 (p = 0.03) and the anti-Ca-Fib3 demonstrated an association with positive FR (p = 0.0012) also refer to the condition of FDR are associated with the presence of anti -Ca-Fib3 (OR 2.976 95% CI: 1.084-8.166 p = 0.034) and with the presence of painful joints (OR 2.28295% CI: 1.047-4.971 p = 0.038) Conclusion: The humoral response in ART may be restricted in part to specific regions of the beta chain of carbamylated fibrinogen, we could consider a future as another biomarker of this disease in a subgroup of patients. Antibody autoantibodies anti-Ca-Fib3 and anti-Ca-Fib2 may be important in subjects with genetic risk (FDR) due to the relationship with inflammatory artifacts that may suggest them to early biomarkers for the development of RA.Mag铆ster en Ciencias Biol贸gicasMaestr铆