Highly sensitive quantification of optic neuritis intrathecal biomarker CXCL13.

BACKGROUND: Elevation of CXCL13, a key regulator of B-cell recruitment in cerebrospinal fluid (CSF) is implicated in multiple sclerosis (MS). OBJECTIVE: to evaluate if measurement of CXCL13 using a highly sensitive assay is of value in acute optic neuritis (ON) patients for the prediction of later MS. METHOD: CXCL13 was measured by Simoa in two independent treatment-naïve ON cohorts, a training cohort (TC, n = 33) originating from a population-based cohort, a validation cohort (VC, n = 30) consecutively collected following principles for population studies. Prospectively, 14/33 TC and 12/30 VC patients progressed to MS (MS-ON) while 19/33 TC and 18/30 VC patients, remained as isolated ON (ION). RESULTS: CXCL13 was detectable in all samples and were higher in ON compared with healthy controls (HC) (p = 0.012). In the TC, CSF levels in MS-ON were higher compared with ION patients and HC (p = 0.0001 and p<0.0001). In the VC, we confirmed the increase of CXCL13 in MS-ON compared to ION (p = 0.0091). Logistic regression analysis revealed an area under receiver operating characteristic curve of 0.83 [95% C.I: 0.73-0.93]. CONCLUSIONS: The highly sensitive CXCL13 Simoa assay demonstrated ability to identify ON patients and separate MS-ON from ION, and predictive diagnostic values indicates a promising potential of this assay.

Predictive values of anti-cyclic citrullinated peptide antibodies and rheumatoid factor in relation to serological aspects of the ACR/EULAR 2010 classification criteria for rheumatoid arthritis.

Objective: In this retrospective population-based register study, we wanted to determine the positive predictive values (PPVs) of immunoglobulin M rheumatoid factor (IgM RF) and anti-citrullinated protein antibodies (ACPAs) at 3 × upper normal limit (UNL), since they are weighted equally in the American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) 2010 criteria for rheumatoid arthritis (RA).Methods: Test results, ordering unit, test date, and patient social security number were collected from the Department of Clinical Immunology at Odense University Hospital from 2007 to 2016 and merged with patient diagnosis from the Danish National Patient Registry.Results: The PPV of IgM RF at 3 × UNL was 14%, compared to a PPV of 43% for ACPAs at 3 × UNL.Conclusion: The PPV of ACPAs is higher than the PPV of IgM RF at 3 × UNL. These findings are not reflected in the ACR/EULAR 2010 classification criteria for RA.

Cerebrospinal fluid biomarkers for predicting development of multiple sclerosis in acute optic neuritis: a population-based prospective cohort study.

BACKGROUND: Long-term outcome in multiple sclerosis (MS) depends on early treatment. In patients with acute optic neuritis (ON), an early inflammatory event, we investigated markers in cerebrospinal fluid (CSF), which may predict a diagnosis of MS. METHODS: Forty patients with acute ON were recruited in a prospective population-based cohort with median 29 months (range 19-41) of follow-up. Paired CSF and serum samples were taken within 14 days (range 2-38), prior to treatment. Prospectively, 16/40 patients were by a uniform algorithm diagnosed with MS (MS-ON) and 24 patients continued to manifest isolated ON (ION) during follow-up. Levels of cytokines and neurofilament light chain (NF-L) were measured at the onset of acute ON and compared to healthy controls (HC). Significance levels were corrected for multiple comparisons ("q"). The predictive value of biomarkers was determined with multivariable prediction models using nomograms. RESULTS: CSF TNF-α, IL-10, and CXCL13 levels were increased in MS-ON compared to those in ION patients (q = 0.021, 0.004, and 0.0006, respectively). MS-ON patients had increased CSF pleocytosis, IgG indices, and oligoclonal bands (OCBs) compared to ION (q = 0.0007, q = 0.0058, and q = 0.0021, respectively). CSF levels of IL-10, TNF-a, IL-17A, and CXCL13 in MS-ON patients correlated with leukocyte counts (r > 0.69 and p < 0.002) and IgG index (r > 0.55, p < 0.037). CSF NF-L levels were increased in ON patients compared to those in HC (q = 0.0077). In MS-ON, a progressive increase in NF-L levels was observed at 7 to 14 days after disease onset (r = 0.73, p < 0.0065). Receiver-operating characteristic (ROC) curves for two multivariable prediction models were generated, with IL-10, CXCL13, and NF-L in one ("candidate") and IgG index, OCB, and leukocytes in another ("routine"). Area under the curve was 0.89 [95% CI 0.77-1] and 0.86 [0.74-0.98], respectively. Predictions of the risk of MS diagnosis were illustrated by two nomograms. CONCLUSIONS: CSF TNF-α, IL-10, CXCL13, and NF-L levels were associated with the development of MS, suggesting that the inflammatory and neurodegenerative processes occurred early. Based on subsequent diagnosis, we observed a high predictive value of routine and candidate biomarkers in CSF for the development of MS in acute ON. The nomogram predictions may be useful in the diagnostic work-up of MS.

Autoimmune and immunogenetic profile of patients with optic neuritis in a population-based cohort.

BACKGROUND: Optic neuritis (ON) is an inflammatory optic neuropathy, where the genetic and autoimmune dependency remains poorly characterized. OBJECTIVE: To investigate autoimmune and immunogenetic aspects of ON. METHOD: In a prospective population-based cohort 51 patients with ON were included. At follow up 20 patients had progressed to multiple sclerosis (MS-ON). All patients were screened for neuronal and systemic autoantibodies. HLA genotypes and allele and genotype frequencies of the PTPN22 C1858T and the PD-1.3 single-nucleotide polymorphisms (SNPs) were determined and compared to a cohort of Danish blood donors, acting as healthy controls. RESULTS: Median follow-up was 366 days (301-430) for MS-ON patients and 375 (range 50-436) for isolated ON (ION). Autoantibodies against myelin oligodendrocyte glycoprotein (MOG-IgG), were positive in two patients, no patients had anti-aquaporin-4 antibodies. Coexisting neural autoantibodies were detected in two patients and in 12 patients other systemic autoantibodies were found. Four (8%) had other autoimmune disorders. A family history of autoimmunity was observed in 12 (24%) and of demyelinating disease in six patients (12%). In MS-ON patients the frequencies of HLA-DQB1*06:02 and HLA-DRB1*15:01 tended to be higher compared to controls (p = 0.08). Stratification of patients with presence of oligoclonal bands (OCB) showed an association to the HLA-DQB1*06:02-HLA-DRB1*15:01 haplotype in ION (HLA-DQB1*06:02 and HLA-DRB1*15:01 (p = 0.03)), and in MS-ON patients (HLA-DQB1*06:02 and HLA-DRB1*15:01 (p = 0.03)). No significant associations to PTPN22 1858C/T or PD-1.3 G/A were found in any group comparison. CONCLUSIONS: ON patients had a general susceptibility to autoimmunity and two were MOG-IgG positive. HLA-DQB1*06:02 and HLA-DRB1*15:01 were associated with the presence of OCB in ON patients.

Magnetic resonance imaging findings at the first episode of acute optic neuritis.

BACKGROUND: Optic neuritis (ON) is a focal demyelinating event, which may evolve into multiple sclerosis (MS). OBJECTIVE: To study MRI characteristics in the acute phase of the first ON episode. METHODS: A prospective population-based study was performed on 31 patients with a first episode of acute ON with a one year follow-up. MRI, clinical evaluation, and detection of aquaporin-4 (AQP4)-IgG and myelin oligodendrocyte glycoprotein (MOG)-IgG was undertaken. For lesion characterization on MRI the optic nerves were divided into three segments: intra-orbital (IO), canalicular (CAN) and chiasmal (CHI). RESULTS: Lesions of the optic nerve were observed in 80.6%(25/31), with IO location in 48%(12/25), CAN in 8% (2/25) and both IO and CAN in 44%(11/25). Patients who converted to MS had lesions located at IO in 77%(10/13), whereas the group with isolated ON had IO and CAN in 73% (8/11), p = 0.003. Brain lesions were observed in 84% (21/25) at onset of ON; 62%(13/25) progressed to MS with more frequent location in brainstem (p = 0.030) and lesions in periventricular areas (p = 0.015). Spinal cord lesions were detected only in patients who progressed to MS (p = 0.002). MOG-IgG was detected in one patient with an optic nerve lesion located at IO and CAN. Serum AQP4-IgG was detected in none. Follow-up MRI showed progression in optic nerve lesions in 55% (11/20) patients. CONCLUSIONS: Specific location of optic nerve and brain lesions and the presence of spinal cord lesions in the acute phase of the first ON episode facilitated an MS diagnosis. The extension of optic nerve lesions following ON suggests a long-term progressive degeneration as an important element of ON pathology.

A population-based prospective study of optic neuritis.

BACKGROUND: Optic neuritis (ON) is often associated with multiple sclerosis (MS). Early diagnosis is critical to optimal patient management. OBJECTIVE: To estimate the incidence of acute ON and the rates of conversion to MS and antibody-mediated ON. METHOD: Population-based prospective study was performed in patients with ON from three ophthalmological departments and 44 practicing ophthalmologists from 2014 to 2016. Ophthalmological and neurological examination, magnetic resonance imaging (MRI), determination of aquaporin-4(AQP4)-IgG and myelin-oligodendrocyte glycoprotein (MOG)-IgG were investigated blindly. RESULTS: In all, 63 patients were evaluated and 51 fulfilled the criteria for ON. All were Caucasian, with female:male ratio of 2.2:1 and a median age of 38 years (16-66); 44 (86%) had a single episode of ON (four bilateral), while 7/51 (14%) had recurrent ON. The overall age-specific incidence was 3.28 (2.44-4.31) per 100,000 person years, 2.02 for men and 4.57 for women. At follow-up, 20 patients met the diagnostic criteria for MS, MRI lesions disseminated in space and time in 17/20 patients. AQP4-IgG was detected in none, MOG-IgG was detected in two patients. CONCLUSION: The prospective incidence of ON was estimated. MRI enabled a diagnosis of MS in a subgroup of patients. Antibody-mediated ON with specificity for MOG was detected in 4% of cases.

HLA, PTPN22 and PD-1 associations as markers of autoimmunity in neuromyelitis optica.

BACKGROUND: Neuromyelitis optica (NMO) is a disease with autoimmune characteristics. A genetic autoimmune dependency for NMO has not been clarified in detail. OBJECTIVE: To investigate immunogenetic aspects of NMO. METHODS: Forty-one patients with NMO and 42 patients with multiple sclerosis (MS) were diagnosed in a population-based Caucasian cohort. HLA DQA1, DQB1, and DRB1 alleles were determined. Polymorphisms in programmed death 1 (PD-1) PD-1.3 G/A and protein tyrosine phosphatase non-receptor 22 (PTPN22) 1858 C/T were genotyped. RESULTS: In the NMO group 15% had other autoimmune disorders and 39% had family occurrence of autoimmunity, comparable to MS. A higher frequency of a family history (17%) of NMO and MS was found in the NMO group (p < 0.026). The frequency of HLA-DQB1*0402 allele was increased in NMO (p after Bonferroni correction, cp < 0.035) and the HLA-DRB1*15 and DQB1*06 alleles were increased in MS (cp < 0.0027, cp < 0.01), compared to controls. No associations of the PTPN22 1858 T were detected. The PD-1.3A allele was increased both in NMO (p < 0.0023) and in MS patients (p < 0.028) compared to controls. CONCLUSION: Patients with NMO had frequent co-existence of autoimmunity and family occurrence of NMO and MS. The PD-1.3A allele was associated with NMO. The data suggest genetic autoimmune dependency of NMO.

A population-based study of neuromyelitis optica in Caucasians.

BACKGROUND: Epidemiologic studies have suggested different prevalence of neuromyelitis optica (NMO) in different ethnic groups. However, data on the incidence and prevalence of NMO in Caucasians are scarce. OBJECTIVE: To estimate the incidence and prevalence of NMO in a predominantly Caucasian population based on the Wingerchuk 2006 criteria. METHODS: The study was a population-based retrospective case series with longitudinal follow-up. Patients with multiple sclerosis (MS), optic neuritis (ON), acute transverse myelitis (TM), and NMO from the 4 neurology and 3 ophthalmology departments in the Region of Southern Denmark having been diagnosed between 1998 and 2008 were investigated. Patients were included based on 1) episodes of ON or TM and 2) an initial brain MRI not diagnostic for MS. An immunofluorescence assay was used to determine aquaporin-4 (AQP-4) antibodies. RESULTS: A total of 477 patients with MS, TM, or ON were evaluated: 163 fulfilled the inclusion criteria, 42 (26%) qualified for the diagnosis of NMO, 26 (62.0%) of these were AQP4 antibody positive. All except one were Caucasian, the female:male ratio was 2.8:1, and mean age at onset was 35.6 years (range 15-64 years). The clinical presentation was heterogeneous including TM, longitudinally extensive TM, ON, and brainstem syndromes. The yearly incidence rate of NMO in the population was estimated to be 0.4 per 10(5) person-years (95% confidence interval [CI] 0.30-0.54) and the prevalence was 4.4 per 10(5) (95% CI 3.1-5.7). CONCLUSIONS: Despite being a rare disease, NMO is more common in a Caucasian population than earlier believed.

Neuromyelitis optica (NMO)--an autoimmune disease of the central nervous system (CNS).

In the past 10 years, neuromyelitis optica (NMO) has evolved from Devic's categorical clinical description into a broader disease spectrum. Serum IgG antibodies have been identified in NMO patients with the water channel aquaporin-4 (AQP4) as their main target antigen. AQP4 antibodies/NMO-IgG have been shown to be a highly specific and moderately sensitive serum biomarker for NMO. The immunopathology of NMO lesions supports that anti-AQP4 antibodies/NMO-IgG are involved in the pathogenesis of NMO. In vitro studies have demonstrated that human NMO-IgG induce necrosis and impair glutamate transport in astrocytes. Certain ethnic groups, notably of Asian and African origin, seem to be more susceptible to NMO than others. The genetic background for these putative differences is not known, a weak human leucocyte antigen association has been identified. AQP4 gene variants could represent a genetic susceptibility factor for different clinical phenotypes within the NMO spectrum. Experimental models have been described including a double-transgenic myelin-specific B- and T-cell mouse. NMO-like disease has been induced with passive transfer of human anti-AQP4 antibodies to the plasma of mice with pre-established experimental autoimmune encephalomyelitis or by intrathecal administration to naive mice. NMO may be characterized as a channelopathy of the central nervous system with autoimmune characteristics.

Sex-specific association of the human PTPN22 1858T-allele with type 1 diabetes.

Type 1 diabetes (T1D) is a common organ-specific autoimmune disease of complex aetiology, involving the interaction of a large number of disease-associated genes. By comparison of a Danish population sample of 253 Caucasian children and adolescents with T1D and a control group consisted of 354 unrelated healthy blood donors, the present study provides evidence of an isolated association of the disease-associated PTPN22 1858T-allele with T1D to the female sex. Furthermore, the present data suggest that PTPN22 genotypes affect the age of onset in a sex-specific manner. The increased frequency of the risk allele and its association with age at onset in female T1D children and adolescents indicates that the genetic contribution to disease pathogenesis is more prominent in females in this population of Danish patients.

Expression of human PTPN22 alleles.

Considering the female predominance in most of the autoimmune disorders that associate with the PTPN22 Trp620 variant and the complexity by which this variant influences immunologic tolerance, the objective of this study was to ascertain if the allele-specific expression of the disease-associated Arg620Trp polymorphism is affected by cis-acting or sex-specific trans-acting factor/s (e.g. sex-hormones). The use of the allele-specific transcript quantification of the Arg620Trp encoding 1858T polymorphism revealed no difference in the expression of the 1858C- and T-alleles in non-stimulated peripheral blood mononuclear cells (PBMCs) from non-pregnant female subjects, male subjects or pregnant female subjects in first or third trimester (P=0.70), respectively. While the transcription of PTPN22 in anti-CD3/anti-CD28 stimulated PBMCs increased fourfold (P<0.0001) and 13-fold (P<0.0001) after 48 and 72 h of activation, respectively, the expression of PTPN22 1858C- and T-alleles increased to the same extent (P=0.64). The present result essentially excludes such phenomena as a partial explanation for the female predominance in most of the autoimmune disorders that associate with the PTPN22 Trp620 variant.

Peroxisome proliferator-activated receptor alpha, delta, gamma1 and gamma2 expressions are present in human monocyte-derived dendritic cells and modulate dendritic cell maturation by addition of subtype-specific ligands.

It has recently been shown by Chang et al. (J Immunol 2000;165:3584-91) that the maturation of dendritic cells (DC) in the presence of long-chain fatty acids redirects DC into Th0/Th2-inducing cells suggesting the involvement of a receptor for long-chain fatty acids like members of the peroxisome proliferator-activated receptors (PPAR) superfamily. Here, we show that immature and mature monocyte-derived DC (Mo-DC) express PPARalpha, PPARdelta, PPARgamma1 and PPARgamma2 mRNA with the highest level of PPARgamma1 mRNA. We were only able to observe the expression of PPARgamma1 protein by Western blotting probably because the protein level of the other subtypes is below the detection limit. Synthetic ligands specific for PPARalpha, PPARdelta or PPARgamma added at day 0-6 have similar effect on the maturation of Mo-DC driving the maturation of Mo-DC with atypical phenotype, reduced expression of IL-10, IL-12 p35 and IL-12 p40 mRNA and with reduced stimulatory effects in mixed leucocyte reaction (MLR). Our data suggest that naturally occurring PPAR ligands like fatty acids and fatty acid derivates have anti-inflammatory effects by redirecting DC into a less stimulatory mode.

Serum concentration of the growth medium markedly affects monocyte-derived dendritic cells' phenotype, cytokine production profile and capacities to stimulate in MLR.

We have investigated how the maturation of monocyte-derived dendritic cells (Mo-DC) is affected by the serum concentration of the culture medium. Day 6 DC cultured in 1% human serum were a heterogeneous population of CD1a(-) and CD1a(+) DC that were separated by flow sorting. In contrast, Mo-DC generated in 10% human serum formed a homogenous population of CD1a(-) cells. Other phenotypically immature characteristics also varied, and three subsets were still distinguishable upon maturation in LPS. Furthermore, CD1a(-) DC and CD1a(+) DC from 1% culture conditions were excellent stimulators in MLR, while DC cultured in 10% serum were poor stimulators. Similarly, different cytokine profiles of the three subsets were identified. DC cultured in 1% serum had low expression of interleukin-12 (IL-12) p40 and IL-10 mRNA at day 6. Upon maturation, expression of IL-12 p40 mRNA was upregulated in CD1a(+) DC, whereas the level remained relatively low in CD1a(-) DC. In contrast, DC cultured in 10% had high levels of IL-10 mRNA at day 6 that was downregulated upon maturation. We conclude that the differentiation of monocytes into DC is significantly influenced by the serum concentration of the growth medium with effects on phenotype, cytokine profile and stimulatory activity.

Autoantibodies and self-reported health complaints in relatives of systemic lupus erythematosus patients: a community based approach.

First-degree relatives (FDRs) and spouses to a population-derived cohort of lupus patients were investigated for the occurrence of selected autoantibodies and self-reported health complaints. A healthy reference population was included. The lupus population consisted of 103 index cases. A total of 275/375 available relatives accepted to enter the study. Two hundred and twenty-six/315 (72%) were FDRs and 49/60 (82%) were spouses. Serum was analysed for ANA using indirect immunofluorescence on Hep-2 cells at the following dilutions: 1:40, 1:80 and 1:160 and in addition sera were tested for anti-dsDNA, IgM RF, ACA (IgM, IgG), anti-beta2GPI (IgM, IgG) and antibodies to prothrombin. ANA positivity occurred more frequently in FDRs compared with spouses and controls at serum dilution 1:160 (10 versus 0% and 2.5%, respectively, P = 0.04 and P < 0.01), 1:80 (24 versus 4% and 5%, respectively, P = 0.003 and P < 0.001) and 1:40 (31 versus 10% and 10%, respectively, P = 0.006 and P < 0.0001). ANA positivity in FDRs occurred randomly, irrespective of family relationship. Fifty-three/184 versus 2/32 FDRs to patients with definite SLE (D-SLE) and incomplete SLE (I-SLE), respectively, tested ANA positive at 1:80 (P < 0.05). FDRs with ANA titer at 80 were affiliated to lupus probands with high SLICC scores (P < 0.05). Self-reported health complaints, cardiovascular/thromboembolic events in particular, were more frequent among FDRs than in spouses. The population-based approach adopted in the present study supports previous clinic-based evidence of an increased propensity for autoantibody occurrence in relatives to SLE patients. In FDRs, present ANA positivity was associated with increased prevalence of health complaints and ANA positivity in FDRs was related to the criterial burden and cumulated damage in corresponding lupus probands. The low ANA frequency among spouses of SLE patients argues against a significant autoantibody triggering effect of shared environment in adult life.

A putative regulatory polymorphism in PD-1 is associated with nephropathy in a population-based cohort of systemic lupus erythematosus patients.

The association between polymorphisms in the programmed death (PD-1) gene and susceptibility to systemic lupus erythematosus (SLE) was determined using genomic DNA, isolated from a population-based cohort of 95 SLE patients and 155 healthy controls. Polymorphisms in the complete PD-1 gene except the large intron 1 were detected by sequencing. Furthermore, the patients were stratified according to the presence or absence of lupus nephropathy. The influence of the detected single nuclear polymorphisms (SNPs) on this specific clinical disease parameter was determined. In total, we identified 12 single nucleotide polymorphisms, of which six were novel and eight were considered to be rare (the frequency of the minor allele of these was less than 1% in our study populations). We found a significant association of an intronic 6867C/G SNP in the PD-1 gene with the presence of lupus nephropathy. As the 6867C/G SNP is located in a putative binding site for the transcriptional repressor ZEB, the associated allele of this SNP potentially alters the transcriptional regulation of PD-1. This report, for the first time, indicates that a 6867C/G SNP of the PD-1 gene is associated with lupus nephropathy in Caucasian SLE patients.

Association of a putative regulatory polymorphism in the PD-1 gene with susceptibility to type 1 diabetes.

The immunoreceptor programmed cell death-1 (PD-1) is reported to play an important role in the regulation of peripheral tolerance in rodents, and it was recently shown that a polymorphism in a regulatory site of the PD-1 gene is associated with susceptibility to the autoimmune disease systemic lupus erythematosus (SLE) in humans. We investigated the existence of single-nucleotide polymorphisms (SNPs) in the PD-1 gene in patients with type 1 diabetes in comparison with healthy control subjects, by analyzing 94 children and adolescents with type 1 diabetes diagnosed before their eighteenth birthday (male : female = 52 : 42) and 155 control subjects. Polymorphisms in the complete PD-1 gene (minus the large intron 1) were detected by sequencing. In total, we identified 14 SNPs, of which six have been previously described, including an intronic 7146G/A SNP. We found this polymorphism to be associated with the development of type 1 diabetes [found in 12.2% of diabetic individuals vs 6.8% in controls; odds ratio (OR) = 1.92]. The associated allele is previously shown to alter a transcription factor-binding site (RUNX1/AML1), and the results of this study suggest that this allele could act as an additional susceptibility allele to type 1 diabetes.

Allelic variation of the inducible costimulator (ICOS) gene: detection of polymorphisms, analysis of the promoter region, and extended haplotype estimation.

The human chromosome region 2q33 including the three costimulatory molecules CD28, CTLA-4 and ICOS, has been subject to much attention due to its linkage to a number of autoimmune diseases. The search for the causal relationship of this linkage has revealed several polymorphisms, but no variations in the amino acid sequences, except for one polymorphism in the leader sequence of CTLA-4. In the present study, we examined the ICOS gene of an unrelated group of healthy donors from the Danish population. We were able to report 16 intronic SNP, one intronic G-insert and two repeat regions in intron 4, consistent with the [T]n and the [GT]n regions reported in a Japanese study. Putative haplotypes for the established SNP and repeat polymorphisms have been estimated by computational analysis. Sequencing of approximately 3500 bp of the upstream region of ICOS revealed an additional eight SNP of which two resided in putative NF-kB and Sp1 sites. In accordance with previous studies we detected no variations in the coding regions except for a rare polymorphism that was found in one donor in the last codon of exon 5, which lead to a heterozygous genotype, but no amino acid change. This suggests that regulation of transcription rather than protein structure could be a possible mechanism in the explanation of linkage.

Leukocyte-depletion of blood components does not significantly reduce the risk of infectious complications. Results of a double-blinded, randomized study.

Allogeneic blood transfusions are claimed to be an independent risk factor for postoperative infections in open colorectal surgery due to immunomodulation. Leukocyte-depletion of erythrocyte suspensions has been shown in some open randomized studies to reduce the rate of postoperative infection to levels observed in nontransfused patients. Using a double-blinded, randomized design, we studied the postoperative infection rate in patients undergoing open colorectal surgery transfused with either leukocyte-depleted erythrocyte suspensions (LD-SAGM) or non-leukocyte-depleted erythrocyte suspensions (SAGM). Unselected patients (n 279) were allocated to receive LD-SAGM (n 139) or SAGM (n 140) if transfusion was indicated. Forty-five percent were transfused, yielding 48 patients in the LD-SAGM group and 64 in the SAGM group. Thirteen patients were excluded because they received one type of transfusion in spite of randomization to the other type. No significant differences in the rates of postoperative infections (P=0.5250) or postoperative complications (P=0.1779) were seen between the two transfused groups. Infection rates were 45% and 38% in the transfused groups and 21% and 23% in the nontransfused groups. No significant difference between the transfused groups was seen on any single infectious event, mortality rate, or duration of hospitalization. Leukocyte-depletion of erythrocyte suspensions transfused to patients undergoing open colorectal surgery does not reduce postoperative infection rates.