Peanut oral immunotherapy modifies IgE and IgG₄ responses to major peanut allergens

详细信息    查看全文

• 作者：Brian P. Vickery ; MD^a ; ^&lowast ; ; ^{bvickery@email.unc.edu} ; Jing Lin ; PhD^b ; Michael Kulis ; PhD^a ; ^&lowast ; ; Zhiyan Fu ; PhD^b ; Pamela H. Steele ; MSN ; CPNP^a ; ^&lowast ; ; Stacie M. Jones ; MD^c ; Amy M. Scurlock ; MD^c ; Gustavo Gimenez ; BSc^b ; Ludmilla Bardina ; MSc^b ; Hugh A. Sampson ; MD^b ; A. Wesley Burks ; MD^a ; ^&lowast ;
• 关键词：Peanut allergy ; oral immunotherapy ; IgE ; IgG4 ; peptide microarray ; epitope ; B cell ; antibody affinity
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2013
• 出版时间：January, 2013
• 年：2013
• 卷：131
• 期：1
• 页码：128-134.e3
• 全文大小：1040 K

文摘

| Figures/TablesFigures/Tables | ReferencesReferences

Background

Patients with peanut allergy have highly stable pathologic antibody repertoires to the immunodominant B-cell epitopes of the major peanut allergens Ara h 1 to 3.

Objective

We used a peptide microarray technique to analyze the effect of treatment with peanut oral immunotherapy (OIT) on such repertoires.

Methods

Measurements of total peanut-specific IgE (psIgE) and peanut-specific IgG₄ (psIgG₄) were made with CAP-FEIA. We analyzed sera from 22 patients with OIT and 6 control subjects and measured serum specific IgE and IgG₄ binding to epitopes of Ara h 1 to 3 using a high-throughput peptide microarray technique. Antibody affinity was measured by using a competitive peptide microarray, as previously described.

Results

At baseline, psIgE and psIgG₄ diversity was similar between patients and control subjects, and there was broad variation in epitope recognition. After a median of 41 months of OIT, polyclonal psIgG₄ levels increased from a median of 0.3 ¦Ìg/mL (interquartile range [25 % to 75 % ], 0.1-0.43 ¦Ìg/mL) at baseline to 10.5 ¦Ìg/mL (interquartile range [25 % to 75 % ], 3.95-45.48 ¦Ìg/mL; P?<?.0001) and included de novo specificities. psIgE levels were reduced from a median baseline of 85.45 kU_A/L (23.05-101.0 kU_A/L) to 7.75 kU_A/L (2.58-30.55 kU_A/L, P?<?.0001). Affinity was unaffected. Although the psIgE repertoire contracted in most OIT-treated patients, several subjects generated new IgE specificities, even as the total psIgE level decreased. Global epitope-specific shifts from IgE to IgG₄ binding occurred, including at an informative epitope of Ara h 2.

Conclusion

OIT differentially alters Ara h 1 to 3 binding patterns. These changes are variable between patients, are not observed in control subjects, and include a progressive polyclonal increase in IgG₄ levels, with concurrent reduction in IgE amount and diversity.