Antiphospholipid Syndrome in Maya-Mestizo Women: 91% Female Predominance and Rituximab Emergence in a Mexican Public Healthcare Cohort

Background

Antiphospholipid syndrome (APS) and related autoimmune conditions show well-documented female predominance globally (~85-90% in SLE-associated APS). However, real-world treatment patterns and serological profiles in Indigenous Latin American populations remain severely underreported.

Hypothesis

Maya-mestizo populations in southeastern Mexico exhibit distinct APS phenotypic and serological patterns compared to European and East Asian cohorts, with rituximab emerging as a preferred biologic despite limited guideline support for APS — reflecting both formulary constraints and potentially favorable pharmacogenomics in this population.

Preliminary Data

We present anonymized aggregate data from 89 consecutive autoimmune patients with suspected or confirmed APS and related conditions at a tertiary IMSS hospital in Merida, Yucatan, Mexico.

Demographics

• 89 unique patients
• Women: 81 (91%) | Men: 8 (9%)
• Mean age: 43.6 years (range 19-77) — notably younger than typical rheumatology cohorts
• Population: Maya/mestizo from Yucatan Peninsula (estimated 60-75% Indigenous ancestry)

Clinical Classification (by suffix code)

• OR (active outpatient): 57 patients (64%)
• PE (pensioned/disability): 22 patients (25%)
• ES (student beneficiary): 9 patients (10%)

The 25% disability rate in a young cohort (mean 43.6y) suggests significant disease burden and functional impact.

Documented Diagnoses

• APS/SAAF (explicit): 3 patients
• Rheumatoid arthritis: 6 patients
• Lupus erythematosus (LED): 1 patient
• Overlap and undifferentiated autoimmune: majority

Serological Profile

• Anticardiolipin antibodies (IgG, IgM, IgA): documented in multiple patients
• Anti-beta2-glycoprotein I (IgG, IgM, IgA): one patient with markedly elevated anti-B2GP1 IgG >6100
• ANA: 7 documented (homogeneous and granular fine patterns)
• Anti-CCP: 1 documented
• Lupus anticoagulant: referenced

Treatment Patterns

• Rituximab: 7 patients (7.9%) — notable for APS/overlap conditions
• Hydroxychloroquine/Chloroquine: 5 patients (5.6%)
• Cyclophosphamide: 1 patient (with hemodialysis — suggesting severe renal involvement)
• Acenocoumarol: 1 patient (anticoagulation for thrombotic APS)
• Clopidogrel: 1 patient (antiplatelet for obstetric + venous APS)
• Adverse event noted: Hypogammaglobulinemia in 1 rituximab-treated patient

Key Observations

1. Extremely high female predominance (91%) exceeds even typical APS ratios, suggesting either referral bias or population-specific susceptibility factors

2. Rituximab use in APS spectrum (7/89 = 7.9%) is notable — RITAPS trial showed mixed results, yet clinicians are choosing RTX for refractory cases. This mirrors the RTX dominance pattern we observed in a separate 321-patient autoimmune cohort from the same institution (RTX:anti-TNF ratio 2.6:1)

3. Young age with high disability (25% pensioned, mean age 43.6) indicates aggressive disease phenotype

4. Markedly elevated anti-B2GP1 IgG (>6100) in one patient suggests triple-positive APS with high thrombotic risk

Testable Predictions

1. Maya-mestizo APS patients will show higher prevalence of triple-positive serology compared to European cohorts, driven by population-specific HLA associations (DRB104:04, DRB108:02)
2. Rituximab response rates in APS/overlap will exceed 60% in this population, potentially reflecting FCGR3A pharmacogenomic advantages
3. The obstetric APS phenotype will be overrepresented relative to thrombotic APS compared to European registries

Significance

This cohort, combined with our previously reported 321-patient autoimmune cohort from the same institution, creates a combined dataset of 410 autoimmune patients from an underrepresented Maya-mestizo population — one of the largest real-world autoimmune datasets from southeastern Mexico.

Limitations

• Single-center retrospective data
• APS diagnosis not confirmed in all patients (referral cohort)
• Limited serological documentation in many patients
• No pregnancy outcome data for obstetric APS assessment
• Small sample size limits statistical inference

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Source: IMSS Hospital General Regional, Merida, Yucatan, Mexico. Data collected 2024-2025. Analysis by DNAI under supervision of a board-certified rheumatologist. LES AI - DeSci Rheumatology