Unraveling Immune Diversity in Latin America:
Insights from the JAGUAR Project and Lupus Research in Mexico
Evelia Lorena Coss-Navarrete 1, Ana Laura Hernández-Ledesma 1, Diego Ramírez-Espinosa 1, Alejandra Schäfer 1, Grecia Sevilla-Parra 1, Tarran Rupall 3, Matiss Ozols 3, Anna Lorenc 3, Carla Jones 3, Tinajero-Nieto Lizbet 4, Torres-Valdez Estefania 5, Peña-Ayala Angélica 4,6, Felix-Rodríguez Guillermo 7, Rosetti-Sciutto Florencia 8, Fernández-Valverde Selene Lizbeth 9, Gutierrez-Arcelus María 10,11,12, Alpízar-Rodríguez Deshiré 13, Gosia Trynka* 2, Alejandra Medina-Rivera* 1.
1: Laboratorio Internacional de Investigación sobre el Genoma Humano (LIIGH-UNAM), Mexico; 2: Escuela Nacional de Estudios Superiores Unidad Juriquilla, Universidad Nacional Autónoma de México, Juriquilla, Querétaro, México; 3: Wellcome Sanger Institute, UK; 4: Hospital General Regional No. 1, Instituto Mexicano del Seguro Social, Querétaro, Santiago de Querétaro, México; 5: Hospital General Regional No. 2, Instituto Mexicano del Seguro Social, El Marqués, México; 6: Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibarra”, Ciudad de México, Mexico; 7: Hospital Star Médica, Querétaro, México; 8: Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México; 9: University of New South Wales (UNSW), Sidney, Australia; 10: Division of Immunology, Boston Children’s Hospital, Boston, MA, USA; 11: Harvard Medical School, Boston, MA, USA; 12 Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA; 13 Centro Medico Althea, Cuernavaca, Morelos, Mexico.
Presenter
MOTIVATION:
AIM: To address how genetic diversity in healthy individuals shapes immunity, resulting in differences in responses to infections and susceptibility to diseases.
STRENGTH: Genetic richness of Latin American populations and environmental diversity.
HOW: The use of single-cell technologies (scRNA-Seq, scATAC-Seq and scCITE-Seq) to identify how diverse ancestries impact gene expression and the composition of immune cells.
STUDY DESIGN:
Figure 2. Methodological approach. Volunteers from Mexico will provide blood samples for PBMC isolation and analysis. Using single-cell technologies (scATAC-seq, scRNA-seq, CITE-seq) and whole genome sequencing (WGS), the study will investigate ancestry’s influence on gene expression and immune cell composition. Health, lifestyle, and environmental data will also be collected.Whole Genome Sequencing (WGS), PBMC: Peripheral blood mononuclear cells.
Volunteers recruitment
RESULTS:
CONCLUSION AND PERSPECTIVES:
Metadata collection with biobank standards
9 : 1
Socioeconomic
Genetics
Environmental
20-40 years old
Highest Lupus Prevalence Among Hispanic Females: 120.7 per 100,000
Ancestry Influences on Lupus Manifestations and Severity
SLE
Chronic
Autoimmune
Multifactorial
Multisystemic
Heterogeneous
Characteristic | SLE (n=104) | Healthy controls (n=121) |
Age (SD) | 39.08 (11.53) | 31.1 (8.54) |
Age range (years old) | 18 - 67 | 18 - 49 |
Years with diagnosis (SD) | 9.15 (8.0) | NA |
SLE family history (n,%) | 27 (25.96%) | NA |
Nephritis (n,%) | 18 (17.31%) | NA |
Disease activity (SLEDAI) Without activity (0 pts) (Zero) Mild activity (1-4 pts) Activity (≧4 pts) | 15 (14.42 %) 16 (15.38%) 73 (70.19%) | NA |
SLEDAI mean score (SD) | 16.30 (16.0) | NA |
Consumption of corticoids (n,%) | 14 (13.46%) | NA |
Daily dose of corticoids (Median, %) | 5 mg (8.65 %) | NA |
Consumption of other treatments (n,%) | 61 (58.65 %) | NA |
Systemic Lupus Erythematosus
Demographic Overview of Study Participants
This project was supported by the Chan-Zuckerberg Initiative (CZI). We thank LAVIS members Luis Aguilar, Alejandro León, and Jair García, and LIIGH members Carina Uribe Díaz, Alejandra Castillo Carbajal, and Christian Molina Aguilar for their support. Ana Laura Hernández-Ledesma, a doctoral student from UNAM, received fellowship CVU/Becario (711015/790972) from CONAHCYT. Evelia Coss is postdoctoral from CONAHCYT (CVU 781634). I sincerely appreciate Mauricio Guzmán, Paty Rodil Garcia, and Andy Bermeo de Jesus for their invaluable help on social media. My heartfelt gratitude goes to Mariana Villegas, Nadia Estrada, Sofia Hernandez, and Francisco Ramirez for their dedication in sampling and blood collection. We also thank the Blood Bank of Querétaro, especially Dr. Said González and Dr. Mercedes.
ACKNOWLEDGEMENTS:
Figure 1. Geographic distribution of individuals with Systemic Lupus Erythematosus in Mexico (n=1172). Graph by: Ana Hernández-Ledesma from LupusRGMX [1, 2].
COMMUNITY ENGAGEMENT:
Single Cell Omics
PBMC collection & genetic profiling
PBMC isolation
scRNA-seq scATAC-seq scCITE-seq
WGS
PBMC isolation from volunteers
Number of SLE patients
[1] Jiwrajka N & Anguera MC. 2022. J Exp Med. PMID: 35510951
[2] Izmirly PM, et al. 2021. Arthritis Rheumatol. PMID: 33474834
Both Conditions
Only SLE
Metadata
General information
Lifestyle
Medical history
Environmental variables
Comorbidities
Medication use
Time since diagnosis
Age at diagnosis
Reproductive health
Sleep quality
Physical activity
Figure 3. Geographic distribution of study participants.. A) Geographic distribution of participants. B) Sex distribution of healthy controls and SLE patients. C) Age group distribution in both groups. yo: years old.
REFERENCES:
Figure 4. Clinical and diagnostic characteristics of SLE patients. A) Distribution of patients across healthcare centers. B) Diagnosis time. C) Distribution of medications used. D) Presence of comorbidities.
Clinical and Diagnostic Characteristics of SLE Patients
Grandparents' Ancestry
Figure 5. Ancestry distribution of participants based on their grandparents' origin.
We aim to recruit 200 healthy volunteers and 200 SLE patients. Join us!
Internal use