# MONONUCLEAR PHAGOCYTE FUNCTION IN IMMUNOLOGIC DISEASES

> **NIH NIH R01** · HOSPITAL FOR SPECIAL SURGERY · 1992 · $224,674

## Abstract

In the past five years there has been a marked increase in our knowledge of
human Fc-gamma receptors which we now understand as three families of
related, but richly diverse, molecules.  The various FC-gammaR forms,
isoforms and allelic forms, -- have different functional capacities.  These
advances bring into focus our hypotheses: 1) that abnormal Fc-gammaR
function (both genetically determined and disease-acquired) is a
contributory factor in autoimmune immune complex disease pathogenesis; 2)
that the presence/ expression of different FC-gammaR structural forms is
both genetically determined (at the level of allelic forms) and under
differential regulational control (at the level of family and isoform
expression); 3) that the different capacities of the Fc-gammaR forms
preferentially associated with or expressed in immunogenetically defined
normals and in SLE patients contributes substantially to the abnormal Fc-
gammaR function.

Preliminary data indicate that the Fc-gammaRI is a compelling candidate
responsible for Fc-gammaR dysfunction in immunogenetically defined normals
and SLE.  Receptor specific studies have shown that Fc-gammaRI is uniquely
associated with this Fc-gammaR abnormality which may be related to newly
discovered Fc-gammaRI isoforms and allelic
forms.  Therefore, the specific aims of this proposal are:
1.  to define the different structural isoforms and allelic forms of Fc-
gamma receptors, focussing on FC-gammaRI;
2.  to define the functional capacities of each of these structural forms;
3.  to define the mechanisms mediating these different functional
capacities;
4.  to define the relative expression of the families and their isoforms
in, and to determine the association of allelic forms with, Fc-y receptor
dysfunction in immunogenetically defined normals and in autoimmune diseases
such as SLE.

The efficiency of handling immune complexes by Fc-gamma receptors is
critical in determining the predisposition to immune complex disease. Thus,
genetically associated abnormalities in Fc-gamma receptor specific function
may be a significant risk factor for SLE.  This proposal will focus on
fundamental Fc-gamma receptor structure-function relationships, emphasizing
the Fc-mediated defects in phagocyte function, so that we can assess the
impact of Fe-gamma receptor polymorphisms on immune complex interactions.
Identification of genetic risk factors for SLE and appropriate regulation
of specific Fc-gamma receptor isoform expression with cytokines or other
agents will allow novel and effective therapy in SLE.

## Key facts

- **NIH application ID:** 3156479
- **Project number:** 2R01AR033062-09
- **Recipient organization:** HOSPITAL FOR SPECIAL SURGERY
- **Principal Investigator:** Robert P. Kimberly
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $224,674
- **Award type:** 2
- **Project period:** 1984-09-30 → 1997-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156479

## Citation

> US National Institutes of Health, RePORTER application 3156479, MONONUCLEAR PHAGOCYTE FUNCTION IN IMMUNOLOGIC DISEASES (2R01AR033062-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3156479. Licensed CC0.

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