Human Anti-Human LAIR1 monoclonal Antibody, clone SFB558 [PE]

Background: Severe malarial anaemia (SMA) is a leading cause of childhood mortality in holoendemic Plasmodium falciparum regions. Methods: To gain an improved understanding of SMA pathogenesis, whole genome and transcriptome profiling was performed in Kenyan children (n= 144, 3-36 months) with discrete non-SMA and SMA phenotypes. Leukocyte associated immunoglobulin like receptor 1 (LAIR1) emerged as a predictor of susceptibility to SMA (P < 1 x10(-2), OR: 0.44-1.37), andwas suppressed in severe disease (-1.69-fold, P=0.004). To extend these findings, the relationship between LAIR1 polymorphisms [rs6509867 (16231C>A); rs2287827 (18835G>A)] and clinical outcomes were investigated in individuals (n= 1512, <5 years) at enrolment and during a 36-month longitudinal follow-up. Findings: Inheritance of the 16,231 recessive genotype (AA) increased susceptibility to SMA at enrolment (OR= 1.903, 95% CI: 1.252-2.891, P= 0.003), and longitudinally (RR= 1.527, 95% CI: 1.119-2.083, P= 0.008). Carriage of the 18,835 GA genotype protected against SMA cross-sectionally (OR = 0.672, 95% CI: 0.480-0.9439, P = 0.020). Haplotype carriage (C16231A/G18835A) also altered cross-sectional susceptibility to SMA: CG (OR = 0.717, 95% CI: 0.527-0.9675, P = 0.034), CA (OR = 0.745, 95% CI: 0.536-1.036, P = 0.080), and AG (OR = 1.641, 95% CI: 1.160-2.321, P = 0.005). Longitudinally, CA carriage was protective against SMA (RR = 0.715, 95% CI: 0.554-0.923, P = 0.010), while AG carriage had an additive effect on enhanced SMA risk (RR = 1.283, 95% CI: 1.057-1.557, P = 0.011). Variants that protected against SMA had elevated LAIR1 transcripts, while those with enhanced risk had lower expression (P < 0.05). Inheritance of 18,835 GA reduced all-causemortality by 44.8% (HR= 0.552, 95% CI: 0.329-0.925, P= 0.024), while AG haplotype carriage increased susceptibility by 68% (HR = 1.680, 95% CI: 1.020-2.770, P= 0.040). Interpretation: These findings suggest LAIR1 is important formodulating susceptibility to SMA and all-cause childhood mortality. (C) 2019 Published by Elsevier B.V.

Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, responsible for approximately 90-95% of cases. We previously reported a novel method that enables direct extraction of extracellular vesicles (EVs) from surgically resected viable tissues, yielding what we term tissue-exudative extracellular vesicles (Te-EVs). Quantitative LC/MS analysis identified 3,871 proteins in Te-EVs, among which leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) was highly enriched in tumor Te-EVs. In the present study, we found that LAIR1 was significantly upregulated in clinical specimens of human RCC tumor tissues compared to that noted in adjacent non-cancerous renal tissues as determined by quantitative PCR analysis. LAIR1 overexpression resulted in accelerated cell proliferation and tumor growth in RCC cells. Moreover, knockdown of LAIR1 using siRNA significantly inhibited cell proliferation in RCC cells. Mechanistically, LAIR1 upregulated the phosphorylation status of Akt, which in turn increased cell proliferation in RCC cells. In clinical RCC specimens, RCC patients with high LAIR1 mRNA expression showed poor progression-free survival compared to those with low LAIR1 expression. These findings indicate that LAIR1 promotes tumorigenesis in RCC.