Background

Chronic infection with Pseudomonas aeruginosa (P. aeruginosa) is a leading cause of death in patients with cystic fibrosis (CF). Immunobiology of P. aeruginosa infection is complex and not well understood. Chronically infected CF patients generate high levels of antibodies to P. aeruginosa, but this response does not lead to clinical improvement. Therefore, additional studies aimed at identification and understanding of the host factors that influence naturally occurring immune responses to P. aeruginosa are needed. In this investigation, we evaluated the contribution of immunoglobulin GM (γ marker) and KM (κ marker) allotypes to the antibody responses to P. aeruginosa lipopolysaccharide (LPS) O1, O6, O11, and alginate antigens and the broadly-conserved surface polysaccharide expressed by many microbial pathogens, poly-N-acetyl-D-glucosamine (PNAG), in 58 chronically infected CF patients.

Methods

IgG1 markers GM 3 and 17 and IgG2 markers GM 23- and 23+ were determined by a pre-designed TaqMan® genotyping assay. The κ chain determinants KM 1 and 3 were characterized by PCR-RFLP. Antibodies to the LPS O antigens, alginate, and PNAG were measured by an ELISA.

Results

Several significant associations were noted with KM alleles. Particular KM 1/3 genotypes were individually and epistatically (with GM 3/17) associated with the level of IgG antibodies to O1, O11, alginate, and PNAG antigens.

Conclusions

Immunoglobulin GM and KM genotypes influence the magnitude of humoral immunity to LPS O, alginate, and PNAG antigens. These results, if confirmed in a larger study population, will be helpful in devising novel immunotherapeutic approaches against P. aeruginosa.

中文翻译：

---

免疫球蛋白 GM 和 KM 同种异型与慢性感染的囊性纤维化患者对铜绿假单胞菌抗原的抗体反应有关

背景

铜绿假单胞菌( P. aeruginosa ) 的慢性感染是囊性纤维化 (CF) 患者死亡的主要原因。铜绿假单胞菌感染的免疫生物学很复杂，而且还不是很清楚。慢性感染的 CF 患者会产生高水平的铜绿假单胞菌抗体，但这种反应不会导致临床改善。因此，需要更多的研究来识别和了解影响对铜绿假单胞菌的自然免疫反应的宿主因素。在这项调查中，我们评估了免疫球蛋白 GM（γ 标记）和 KM（κ 标记）同种异型对铜绿假单胞菌的抗体反应的贡献在 58 名慢性感染的 CF 患者中，脂多糖 (LPS) O1、O6、O11 和藻酸盐抗原以及由许多微生物病原体聚-N-乙酰基-D-葡糖胺 (PNAG) 表达的广泛保守的表面多糖。

方法

IgG1 标记 GM 3 和 17 以及 IgG2 标记 GM 23- 和 23+ 通过预先设计的 TaqMan® 基因分型测定法确定。κ 链决定簇 KM 1 和 3 通过 PCR-RFLP 进行表征。通过ELISA测量LPS O抗原、藻酸盐和PNAG的抗体。

结果

与 KM 等位基因有几个重要的关联。特定的 KM 1/3 基因型单独和上位性（GM 3/17）与针对 O1、O11、藻酸盐和 PNAG 抗原的 IgG 抗体水平相关。

结论

免疫球蛋白 GM 和 KM 基因型影响对 LPS O、藻酸盐和 PNAG 抗原的体液免疫程度。这些结果，如果在更大的研究人群中得到证实，将有助于设计针对铜绿假单胞菌的新型免疫治疗方法。