# The role of RIFINs and their interaction with blood type in vulnerability to severe malaria in Malian children

> **NIH NIH F30** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $39,120

## Abstract

PROJECT SUMMARY/ABSTRACT
Plasmodium falciparum causes nearly 435,000 deaths annually worldwide. Victims of severe malaria are
predominantly sub-Saharan children, who may present with symptoms of severe anemia or unarousable coma.
The pathogenesis of severe malaria is poorly understood but mediated by the expression of adhesive variant
surface antigens (VSAs) on infected red blood cells. These VSAs are involved in sequestration and rosetting,
unique virulence factors that allow the parasite to evade host immune responses and prevent clearance in the
spleen. In particular, ABO blood groups are critical for rosetting, which is the spontaneous binding of infected
and uninfected erythrocytes together. Individuals with blood type A are particularly vulnerable to severe malaria,
unlike those with blood type O who appear relatively protected against severe disease. A relatively unstudied
family of VSAs, the repetitive interspersed family (RIFIN) proteins, have been recently found to be important in
rosetting. RIFINs preferentially bind blood type A antigens, forming larger and tighter rosettes than in blood type
O. RIFINs may mediate the association between ABO blood type and severe malaria susceptibility; these
proteins also appear to be targets for protective immunity. Humoral immune responses against RIFINs have
been correlated with asymptomatic infections. As such, we posit that a subset of RIFINs play a critical role in
severe malaria pathogenesis and that individuals who lack immunity to this subset are the most susceptible to
develop severe malaria. In a case-control study that began in Mali in 2014, our group collected blood and serum
samples from severe malaria cases and matched controls with uncomplicated malaria. Here, we propose to
identify and sequence RIFINs expressed in severe malaria using next-generation RNA-sequencing technologies.
Using a custom protein microarray, we will then determine whether a lack of antibodies to these RIFIN proteins
is associated with developing severe disease. In Aim 1, we will identify subgroups of RIFIN transcripts that are
differentially expressed in subjects with severe malaria versus matched controls with uncomplicated malaria via
RNA-Seq. We hypothesize that a subset of RIFIN-As will be predominantly expressed in severe malaria cases
with blood type A, in contrast to expression of a heterogeneous group of RIFIN-As in other infections. In Aim 2,
we will use the predominant RIFIN transcripts identified in Aim 1 and other parasite antigens to populate a custom
protein microarray in order to define a subset of RIFIN proteins associated with increased vulnerability to severe
malaria. We hypothesize that sera from children acutely ill with severe malaria will recognize fewer RIFIN proteins
on a protein microarray and react to them less intensely than their convalescent sera and sera from matched
controls with uncomplicated malaria, particularly for severe malaria cases with blood type A. The candidate will
gain...

## Key facts

- **NIH application ID:** 10012761
- **Project number:** 5F30HL146095-02
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Albert E Zhou
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $39,120
- **Award type:** 5
- **Project period:** 2019-08-16 → 2023-08-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10012761

## Citation

> US National Institutes of Health, RePORTER application 10012761, The role of RIFINs and their interaction with blood type in vulnerability to severe malaria in Malian children (5F30HL146095-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10012761. Licensed CC0.

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