CR1 Polymorphisms Research Articles

Complement receptor type 1 and 2 (CR1 and CR2) gene polymorphisms and plasma protein levels are associated with the Dengue disease severity

The pathological outcome of dengue disease results from complex interactions between dengue virus (DENV) and host genetics and immune response. Complement receptor types 1 and 2 (CR1 and CR2) mediate complement activation through the alternative pathway. This study investigated the possible association of genetic polymorphisms and plasma levels of CR1 and CR2 with dengue disease. A total of 267 dengue patients and 133 healthy controls were recruited for this study. CR1 and CR2 gene polymorphisms were analyzed by Sanger sequencing, while plasma CR1 and CR2 levels were measured by ELISA. The frequency of the CR1 minor allele rs6691117G was lower in dengue patients and those with severe dengue compared to healthy controls. Plasma CR1 and CR2 levels were decreased in dengue patients compared to healthy controls (P < 0.0001) and were associated with platelet counts. CR1 levels were lower in dengue patients with warning signs (DWS) compared to those without DWS, while CR2 levels were decreased according to the severity of the disease and after 5 days (T1) and 8 days (T2) of follow-up. CR2 levels were decreased in dengue patients positive for anti-DENV IgG and IgM and patients with bleeding and could discriminate DWS and SD from dengue fever patients (AUC = 0.66). In conclusion, this study revealed a reduction in CR2 levels in dengue patients and that the CR1 SNP rs6691117A/G is associated with the dengue severity. The correlation of CR2 levels with platelet counts suggests that CR2 could be an additional biomarker for the prognosis of severe dengue disease.

First Report of CR1 Polymorphisms and Soluble CR1 Levels Associated with Late Onset Alzheimer's Disease (LOAD) in Latin America.

The CR1 gene has been widely studied in Alzheimer's disease (AD), since its first association with the disease in 2009. Even after 11years of this discovery, the role of this gene in AD has not yet been fully elucidated and the association of its variants was not validated in Latin American populations. We genotyped five CR1 single nucleotide polymorphisms (SNPs rs6656401, rs3849266, rs2274567, rs4844610, and rs12034383) in up to 162AD patients and 137 controls through PCR-SSP and iPLEX MassARRAY Platform (Sequenom), and measured soluble CR1 (sCR1) levels in plasma of 40AD patients and 39 controls with an enzyme-linked immunosorbent assay (ELISA). Homozygosity for haplotype rs3849266*C_rs2274567*A (CA/CA genotype) was associated with susceptibility to AD (OR = 2.94, p = 0.018). Patients presented higher sCR1 levels in plasma than controls (p = 0.038). Furthermore, patients that carry the rs2274567*G allele (p.1208Arg) presented higher sCR1 levels than A/A (p.1208His/His) homozygotes (p = 0.036). This is the first study to validate the association of CR1 polymorphisms with late-onset Alzheimer's disease, as well as to evaluate sCR1 levels in a Latin American population. SNPs present in the regulatory and coding regions of this gene may be playing a key role in the observed association, probably by interfering in Aβ plaques clearance. Inhibition may be due to the increase in local sCR1 levels observed in patients, which may result from polymorphisms leading to larger isoforms of CR1 and/or structural alterations of the protein that makes it less functional, as well as increased vesiculation of the molecules.

Complement Receptor 1 (CR1, CD35) Polymorphisms and Soluble CR1: A Proposed Anti-inflammatory Role to Quench the Fire of "Fogo Selvagem" Pemphigus Foliaceus.

Pemphigus foliaceus is an autoimmune disease that is sporadic around the world but endemic in Brazil, where it is known as fogo selvagem (FS). Characterized by autoantibodies against the desmosomal cadherin desmoglein 1, FS causes painful erosions, and crusts that may be widespread. The recognition of antigens, including exposed sugar moieties, activates the complement system. Complement receptor 1 (CR1, CD35), which is responsible for the Knops blood group on erythrocytes (York and McCoy antigens), is also expressed by antigen-presenting cells. This regulates the complement system by removing opsonized antigens, blocking the final steps of the complement cascade. Membrane-bound CR1 also fosters antigen presentation to B cells, whereas soluble CR1 has anti-inflammatory properties. CR1 gene polymorphisms have been associated with susceptibility to complex diseases. In order to investigate the association of CR1 polymorphisms with FS susceptibility, we developed a multiplex sequence-specific assay to haplotype eleven polymorphisms in up to 367 FS patients and 242 controls from an endemic area and 289 from a non-endemic area. We also measured soluble CR1 (sCR1) in the serum of 53 FS patients and 27 controls and mRNA levels in the peripheral blood mononuclear cells of 63 genotyped controls. The haplotypes CR1*3B2B (with the York antigen–encoded by p.1408Met) and CR1*3A2A (with p.1208Arg) were associated with protection against FS (OR = 0.57, P = 0.027, and OR = 0.46, P = 0.014, respectively). In contrast, the CR1*1 haplotype (with the McCoy antigen – encoded by p.1590Glu) was associated with FS susceptibility (OR = 4.97, P < 0.001). Heterozygote rs12034383*A/G individuals presented higher mRNA expression than homozygotes with the G allele (P = 0.04). The lowest sCR1 levels occurred in patients with active disease before treatment (P = 0.036). Patients in remission had higher levels of sCR1 than did healthy controls (P = 0.013). Among those under treatment, patients with localized lesions also presented higher sCR1 levels than those with generalized lesions (P = 0.0073). In conclusion, the Knops blood group seems to modulate susceptibility to the disease. Furthermore, corticosteroid treatment might increase sCR1 serum levels, and higher levels may play an anti-inflammatory role in patients with FS, limiting the distribution of lesions. Based on these results, we suggest CR1 as a potential new therapeutic target for the treatment of FS.

High Incidence of Malaria Along the Sino-Burmese Border Is Associated With Polymorphisms of CR1, IL-1A, IL-4R, IL-4, NOS, and TNF, But Not With G6PD Deficiency.

Malaria is highly endemic in Yunnan Province, China, with the incidence of malaria being highest along the Sino-Burmese border. The aim of our study was to determine whether genetic polymorphisms are associated with the prevalence of malaria among Chinese residents of the Sino-Burmese border region. Fourteen otherwise healthy people with glucose-6-phosphate dehydrogenase (G6PD) deficiency, 50 malaria patients, and 67 healthy control subjects were included in our cross-sectional study. We analyzed the frequency of the G3093T and T520C single-nucleotide polymorphisms (SNPs) of CR1. Logistic regression was used to calculate the prevalence odds ratio (POR) and 95% confidence interval (CI) of malaria for the T520C SNP of CR1 and SNPs of G6PD, IL-4, IL-4R, IL-1A, NOS, CD40LG, TNF, and LUC7L. The frequency of the 3093T/3093T genotype of CR1 in the malaria group (0.16) was significantly higher than that in the control group (0.045, P < 0.05), and significantly lower than that in the G6PD deficiency group (0.43, P < 0.01). The frequency of the 520T/520T genotype of CR1 was significantly higher in the malaria patients (0.78) than that in the control group (0.67, P < 0.05) and G6PD-deficiency group (0.36, P < 0.05). The T allele of the T520C variant of CR1 was significantly associated with the prevalence of malaria (POR: 1.460; 95% CI: 0.703-3.034). Polymorphisms of G6PD did not significantly influence the prevalence malaria (P > 0.05). A GTGTGTC haplotype consisting of IL-1A (rs17561), IL-4 (rs2243250), TNF (rs1800750), IL-4R (rs1805015), NOS (rs8078340), CD40LG (rs1126535), and LUC7L (rs1211375) was significantly associated with the prevalence of malaria (POR: 1.822, 95% CI: 0.998-3.324). The 3093G/3093G and 520T/520T genotypes are the predominant genetic variants of CR1 among Chinese residents near the Sino-Burmese border, and the T allele of T520C is associated with the prevalence of malaria in this region. Although G6PD deficiency does not protect against malaria, it may diminish the association between malaria and the CR1 polymorphisms in this population. The GTGTGTC haplotype is also associated with the prevalence of malaria in this region.

Effect Modification By Cognition-Related Polymorphisms Of The Association Between Cumulative Lead Exposure And Incident Cognitive Impairment In Older Men

Background: Bone lead is a significant predictor of decline in scores on the Mini Mental Status Exam (MMSE) in older adults, indicating that accumulated lead burden negatively impacts cognitive function. It is unknown if genes associated with Alzheimer's disease and cognitive impairment modify the association between lead and cognitive function. Aims: To evaluate whether APOE (rs429358 and rs7412), PICALM (rs3851179), CLU (rs11136000) CR1 (rs6656401), and CELF1 (rs7933019) polymorphisms found to be associated with Alzheimer's disease in genome-wide association studies modify the association between cumulative lead exposure and incident cognitive impairment defined by having an MMSE score

Extensive Genomic Variability of Knops Blood Group Polymorphisms is Associated with Sickle Cell Disease in Africa

Sickle cell disease (SCD) is a multisystem disorder characterized by chronic hemolytic anemia, vaso-occlusive crises, and marked variability in disease severity. Patients require transfusions to manage disease complications, with complements, directed by complement regulatory genes (CR1) and its polymorphisms, implicated in the development of alloantibodies. We hypothesize that CR1 polymorphisms affect complement regulation and function, leading to adverse outcome in SCD. To this end, we determined the genomic diversity of complement regulatory genes by examining single nucleotide polymorphisms associated with Knops blood group antigens. Genomic DNA samples from 130 SCD cases and 356 control Africans, 331 SCD cases and 497 control African Americans, and 254 Caucasians were obtained and analyzed, utilizing a PCR—RFLP (polymerase chain reaction–restriction fragment length polymorphism) assay. Analyzing for ethnic diversity, we found significant differences in the genotypic and allelic frequencies of Sl1/Sl2 (rs17047661) and McCa/b (rs17047660) polymorphisms between Africans, African Americans, and Caucasians (P < 0.05). The homozygote mutant variants had significantly higher frequencies in Africans and African Americans but were insignificant in Caucasians (80.2% and 59.6% vs 5.9% for Sl1/2; and 36% and 24% vs 1.8% for McCa/b). With SCD, we did not detect any difference among cases and controls either in Africa or in the United States. However, we found significant difference in genotypic (P < 0.0001) and allelic frequencies (P < 0.0001) of Sl1/Sl2 (rs17047661) and McCa/b (rs17047660) polymorphisms between SCD groups from Africa and the United States. There was no difference in haplotype frequencies of these polymorphisms among or between groups. The higher frequency of CR1 homozygote mutant variants in Africa but not United States indicates a potential pathogenic role, possibly associated with complicated disease pathophysiology in the former and potentially protective in the latter. The difference between sickle cell groups suggests potential genetic drift or founder effect imposed on the disease in the United States, but not in Africa, and a possible confirmation of the ancestral susceptibility hypothesis. The lower haplotype frequencies among sickle cell and control populations in the United States may be due to the admixture and the dilution of African genetic ancestry in the African American population.

Meta-analysis of the association between CR1 polymorphisms and risk of late-onset Alzheimer's disease

CR1 polymorphisms have been reported to be associated with late-onset Alzheimer's disease (LOAD) susceptibility. The findings of these studies, however, have been inconsistent. Therefore, we performed a meta-analysis to assess the association between CR1 variants and LOAD susceptibility. We retrieved all relevant studies of the associations between CR1 polymorphisms and the susceptibility to LOAD for the period up to March 30, 2014. The strength of the association between CR1 polymorphisms and LOAD risk was estimated by odds ratios (ORs) and their 95% confidence intervals (CIs). A total of 6 articles were eventually identified with 2752 LOAD cases and 2313 controls for the rs6656401 polymorphism, and 4 studies containing 2547 LOAD cases and 2338 controls were included for the rs3818361 polymorphism. Overall, the pooled data showed that the CR1 rs6656401 polymorphism was significantly associated with LOAD risk in the overall population (A vs. G: OR=1.32, 95%CI=1.17–1.50, P=0.000; AG+AA vs. GG: OR=1.39, 95%CI=1.20–1.61, P=0.000). With respect to the CR1 rs3818361 polymorphism, a statistically significant increased LOAD risk was observed in the overall population (T vs. C: OR=1.24, 95% CI=1.13–1.37, P=0.000; TT+TC vs. CC: OR=1.30, 95% CI=1.15–1.46, P=0.000; TT vs. TC+CC: OR=1.35, 95% CI=1.06–1.71, P=0.014). This meta-analysis demonstrated significant associations of both the CR1 rs6656401 and CR1 rs3818361 polymorphisms with LOAD susceptibility.

CR1 in Alzheimer's disease.

The complement component receptor 1 gene (CR1), which encodes a type-I transmembrane glycoprotein, has recently been identified as one of the most important risk genes for late-onset Alzheimer's disease (LOAD). In this article, we reviewed the recent evidence concerning the role of CR1 in LOAD. First, we introduced the structure, localization and physiological function of CR1 in humans. Afterward, we summarized the relation of CR1 polymorphisms with LOAD risk. Finally, we discussed the possible impact of CR1 on the pathogenesis of AD including amyloid-β pathology, tauopathy, immune dysfunction and glial-mediated neuroinflammation. We hope that a more comprehensive understanding of the role that CR1 played in AD may lead to the development of novel therapeutics for the prevention and treatment of AD.

CR1 and the “Vanishing Amyloid” Hypothesis of Alzheimer’s Disease

CR1 and the “Vanishing Amyloid” Hypothesis of Alzheimer’s Disease

The polymorphism of Knops blood group system in Korean population and their relationship with HLA system

The main purpose of this report is to provide baseline gene frequencies of Knops blood group in the complement receptor 1 gene (CR1) in Korean population. In addition, possible relationship between the CR1 polymorphism and HLA specificities were studied, because the two systems had principal importance in immunity. CR1, which contains Knops antigens, was investigated by PCR-direct sequencing from 238 cord blood from Koreans. HLA data was archived from the enrolled cord blood units. Among the 7 SNPs, only 4843 (for KCAM antigen) and 4223 (for Yk(a)) nucleotide positions showed polymorphism. The genotype frequencies of KCAM were A/A (62.2%), A/G (33.2%), and G/G (4.6%); Yk(a) were C/C (29.4%), C/T (50%), and T/T (20.6%). KCAM (A/A) associated with HLA-DRB1(∗)13 (p=0.003, P(c)=0.0513); KCAM (G/G) with HLA-A(∗)30 (p<0.001, P(c)=0.0012). The Knops blood group system in Korean population has no diversity, except SNPs for KCAM and Yk(a), and the genotype of KCAM related with specific HLA alleles.

Plasmodium falciparum malaria and carbohydrate blood group evolution

Plasmodium falciparum malaria, as ancient as hominid evolution itself, has provoked more change within the human genome than any other pathogen. JBS Haldane observed the overlapping distributions for thalassaemia and malaria endemicity and proposed ‘balanced polymorphisms’ as advantageous heterozygous mutant states. We now appreciate the wider range of haemoglobinopathies, membranopathies, and enzymopathies as distinct evolutionary adjustments to the erythrocyte, the very compartment which P. falciparum hijacks to sicken the host. Unlike other Plasmodium species, P. falciparum’s power over the erythrocyte consists of its limitless red cell infectivity and its capacity to render the infected red blood cell (iRBC) adhesive enough to arrest in the circulation. This latter cytoadhesivity is achieved by sticky knob proteins known as ‘Plasmodium falciparum erythrocyte membrane protein‐1’ (PfEMP‐1), trafficked to the red cell exterior from the parasite within. PfEMP‐1 is designed to latch onto endothelial cells of the post‐capillary venules (‘sequestration’), as well as onto other uninfected red blood cells and platelets (‘rosetting’). In so stalling their flow towards the spleen, the iRBC doubly harms the host by resisting the first defence of reticuloendothelial clearance and congesting the host’s microvasculature. The youngest, most malaria‐naïve suffer malaria’s highest case fatality rates, revealing just how critical this innate (pre‐adaptive) immune control of parasitaemia is. The biochemical means by which PfEMP‐1 achieves its cytoadhesive promiscuity is in part through one particular lectin‐like domain, DBL1α. This domain binds not only to heparan sulphate‐like glycosaminoglycans, but to two blood group antigens expressed densely on erythrocytes: the group A carbohydrate in the ABO system and antigens (including those of the Knops system) on CR1 (CD35). If indeed these ligands are critical in the molecular pathogenesis of malaria fatalities, then we might expect to observe non‐adhesive variants ascending to higher prevalence in the most malaria‐endemic parts of the world. The cytoadhesivity of wildtype group A hosts is theoretically, and in vitro, demonstrably mitigated by what we now know are the mutant phenotypes which define the polymorphisms of the ABO system. These include the group O or B alleles, the weaker A types and the genetics influencing the quantity of secreted (competitive) free A antigen in group A hosts. Each of these phenotypes is observed at higher frequencies in malaria‐endemic areas. Certain CR1 polymorphisms are also more frequently found in these parts of the world. The assembly of in vitro, geographic and clinical evidence weighs heavily towards ABO evolution being a highly specific response to P. falciparum. Rather than bypassing invasion or enhancing clearance, these mutations are special because they highlight the importance of escape from cytoadhesion. Forthcoming are the results of the first prospective study powered to confirm the impact of ABO on malaria mortality (NCT 00707200, http://www.clinicaltrials.gov). Should the results of emerging studies confirm a survival advantage among group O individuals, the basic strategy for transfusion support in malaria may shift to greater use of group O red cells. The clinical value of this approach, more immediately available than any new drug or vaccine development, will need to be tested in clinical trials.

CR1 levels and gene polymorphisms exhibit differential association with falciparum malaria in regions of varying disease endemicity

Complement receptor 1 (CR1/CD35) levels on erythrocytes and related CR1 polymorphisms have been associated with response to falciparum malaria in populations inhabiting malaria-endemic regions. Differences in disease association profiles of its low expression alleles have been observed in populations from different regions of the world. We analyzed the influence of CR1 levels and associated SNPs on susceptibility/resistance to falciparum malaria in Indian populations. Two CR1 SNPs [exon 22 (A/G) and intron 27 (A/T)] define the low expression (L) CR1 allele in populations inhabiting a Plasmodium falciparum–endemic and a nonendemic region of India. Populations of the endemic region have very low red blood cell surface CR1 levels and higher frequencies of the exon 22 and intron 27 mutant L alleles. Whereas low CR1 levels correlated with susceptibility to severe malaria in the nonendemic region, high CR1 levels were associated with manifestation of disease in the endemic region. In addition, the exon 22 L allele was a risk factor for severe malaria in the nonendemic region. Absence of correlation between levels of tumor necrosis factor– α, interferon-γ, and interleukin-6 with CR1 levels in patients with severe disease indicated that RBC CR1 levels in individuals are not the major determinants of pro-inflammatory cytokine release during infection. Our results are interpreted in the context of differences in the pathogenesis of severe malaria in the malaria-endemic and nonendemic region.

Analysis of CR1 and CR2 polymorphisms in Italian patients with angiographically documented coronary artery disease (CAD)

Analysis of CR1 and CR2 polymorphisms in Italian patients with angiographically documented coronary artery disease (CAD)

Association of complement receptor 1 (CR1, CD35, C3b/C4b receptor) density polymorphism with glomerulonephritis in Indian subjects

Complement receptor 1 (CR1, CD35, C3b/C4b receptor), a polymorphic membrane bound glycoprotein is important both as a complement regulatory protein, and as a vehicle for immune complex clearance. It is differentially expressed on erythrocytes, eosinophils, monocytes, B and T-lymphocytes, dendritic cells and kidney podocytes. It also occurs in the plasma as soluble CR1 (sCR1) and in urine as urinary CR1 (uCR1). Different population studies have either suggested or refuted the functional and physiological significance of genomic (HH, high erythrocyte CR1 expression; HL, intermediate and LL, low expression) polymorphism of CR1 in health and disease. Prevalence of autoimmune disorders like RA, GN and SLE is higher in Asian–Indians compared to the western world. Although several studies from India emphasize the modulation of E-CR1 levels as a key factor in the pathophysiology of glomerulonephritis (GN), none of them, however, provide much information on the role of CR1 gene variance in this context. We, therefore, carried out the study of CR1 polymorphism in 117 normal Indian subjects and 65 patients suffering from glomerulonephritis in order to study its possible association with the disease and E-CR1 levels. This is the first study of its kind in the Indian population, in which, the direct effect of a particular genotype on the E-CR1 levels and its possible association with the disease has been studied simultaneously.

A CR1 polymorphism associated with constitutive erythrocyte CR1 levels affects binding to C4b but not C3b.

The erythrocyte type one complement receptor (E-CR1) mediates erythrocyte binding of complement-opsonized immune complexes (IC), and helps protect against random deposition of circulating IC. Two linked CR1 polymorphisms occur in binding domains, at I643T and Q981H. In Caucasians, the variant alleles (643T, 981H) are associated with low constitutive E-CR1 expression levels. This study was conducted to determine if these polymorphisms affect ligand binding, and if so, represent risk factors for the autoimmune IC disease, systemic lupus erythematosus (SLE). In an ELISA comparing relative ligand binding differences, E-CR1 from individuals homozygous for the variant residues (643TT/981HH) exhibited greater binding to C4b, but not C3b, than homozygous wild-type E-CR1. Analysis of single-binding domain CR1 constructs demonstrated that the 981H residue imparted this enhanced C4b binding. No differences were observed in the 981H allele frequency between Caucasian controls (0.170, n = 100) and SLE patients (0.130, n = 150, P = 0.133), or between African American controls (0.169, n = 71) and SLE patients (0.157, n = 67). In a subset of individuals assessed for CR1 size, excluding from this analysis those expressing at least one B allele revealed a trend for over-representation of the 981H allele in Caucasian controls (0.231 frequency, n = 26) versus SLE patients (0.139, n = 83, P = 0.089), but again no difference between African American controls (0.188, n = 24) and SLE patients (0.191, n = 34). These data suggest that the 981H residue compensates for low constitutive expression of E-CR1 in Caucasians by enhancing C4b binding. This may contribute protection against SLE.

CR1 polymorphisms associated with SLE

CR1 polymorphisms associated with SLE

Identification of complement receptor one (CR1) polymorphisms in west Africa.

Complement receptor one (CR1) is a ligand for the rosetting of Plasmodium falciparum infected red cells with uninfected cells. Since CR1 exhibits three known polymorphisms, we studied European-Americans (n = 112) and African-Americans (n = 330) and Malians (n = 158) to determine if genetic differences existed in an area endemic for malaria that could offer a survival advantage. The frequencies of Knops blood group phenotypes McC(b+) and Sl(a-) were greatly increased in Africans vs Europeans. Although the frequency of McC(b+) was similar between Africans from the USA or Mali, the Sl(a-) phenotype was significantly higher in Mali (39% vs 65%, respectively). There was an increased frequency of the largest size (250 kD) of CR1 in Mali, but this did not differ significantly from the USA (P = 0.09). Both cohorts of Africans had higher expression of red cell CR1 than European-Americans but this showed little difference between the USA and Mali groups. Thus, the most important CR1 polymorphism relevant to rosetting of malaria infected cells appears to be the Knops blood group.

Influence of glycosylation on allelic and cell-specific Mr variation, receptor processing, and ligand binding of the human complement C3b/C4b receptor.

The human complement C3b/C4b receptor (CR1), a single chain membrane glycoprotein of Mr approximately 200,000, has several cell-specific Mr variations as well as an allelic variation involving four phenotypes whose Mr values span a range of 90,000. We investigated the role of glycosylation in these structural variations and in receptor metabolism. In the human HL-60 promyelocytic leukemic cell line differentiated toward granulocytes or monocytes and in Epstein-Barr virus-transformed B lymphoblastoid cell lines of the common phenotype, CR1 is synthesized as a precursor of Mr = 222,000 that is converted into mature CR1s with differing Mr values. Endoglycosidase F treatment of mature CR1 from all these cell types produced the same lower Mr band. Additionally, the previously noted 5,000 higher Mr of CR1 from human peripheral granulocytes versus erythrocytes was abrogated by endoglycosidase F. Hence these cell-specific variations are due to differences in N-glycosylation. Lectin affinity chromatography shows that these N-linked oligosaccharides are mostly tri- and tetraantennary complex-type species with specific differences in fractionation patterns that correlate with their differing Mrs. In lymphoblastoid cell lines, the four allelic variants each have a precursor 6,000 lower in Mr than the respective mature CR1. In the presence of tunicamycin, each of the CR1 allelic products is 25,000 lower in Mr than the glycosylated receptor. The failure to radiolabel CR1 with [3H]glucosamine in the presence of tunicamycin indicates the lack of O-linked oligosaccharide on CR1. These data, taken together, strongly suggest that the CR1 polymorphism resides at the polypeptide level. Nonglycosylated CR1 synthesized in the presence of tunicamycin had twice the turnover rate of glycosylated CR1. The efficiency of surface membrane insertion and of ligand binding to hemolytically inactive C3 were markedly reduced for nonglycosylated CR1, suggesting that glycosylation is important for the proper expression of CR1 function.