RESUMO
Background: Selective anti-polysaccharide antibody deficiency (SPAD) with CD5 B-cell predominance and autoimmune phenomena was identified in a male cohort first reported by Antall et al in 1999. The phenotypically likewise and genotypically identical X-linked immunodeficiency with magnesium defect, Epstein-Barr Virus infection, and neoplasia (XMEN) disease was defined as a novel primary immunodeficiency (PID) in 2011. Recent studies of the magnesium transporter 1 (MAGT1) gene mutation reveal glycosylation defects contributing to more phenotypic variance than the "XMEN" title pathologies. The updated title, "X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect," was proposed in 2020. Objectives: To reflect the patient population more accurately, a prospective classification update may consider MAGT1 glycobiological errors contributing to phenotypic variance but also pre-genetic testing era reports with CD5 B-cell predominance. Methods: Patient 1 from Antall et al presented at 28 years of age for further immunological evaluation of his CD5/CD19 B-cell predominance diagnosed at 5 years old. Design: Immune re-evaluation done through flow cytometry and next-generation sequencing. Results: Flow cytometry B-cell phenotyping revealed persistent CD5+CD19+ (93%). Flow cytometric histogram quantified reduced activator CD16+CD56+ natural killer and CD8+ T-cell receptor, Group 2, Member D (NKG2D) glycoprotein expression. A c.923-1_934 deletion loss of function mutation was identified in the MAGT1 gene. Conclusion: We suggest the novel PID XMEN, based on its CD5 B-cell predominance, had been discovered and reported over a decade earlier as CD5+ PID based on the MAGT1 mutation found in the same. We encourage consideration of combining these labels and recent findings to offer the most accurate classification of this disease.
RESUMO
Structural skeletal abnormalities are associated with primary immunodeficient (PID) patients. These abnormalities have not been well studied in PID with reference to osteopathic medicine tenets. Osteopathic structural examinations of PID patients with respect to these tenets and the diagnosis of somatic dysfunctions preventing the free flow of lymph fluids back into the circulation and the disruption of the skeletal microenvironment may have an impact on the status of the immune system in patients with a PID. A standardized evaluation was conducted in a patient with a phosphatidylinositol 3-kinase regulatory subunit 1 (PIK3R1) mutation who presented with skeletal abnormalities. A literature review was also conducted to determine the breadth of other PIDs with structural irregularities. Osteopathic structural clinical examinations (OSCEs) were performed by an osteopathic medical student, fellow, and attending after receiving informed consent from the patient. The findings were collected regionally noting severity, tissue texture changes, asymmetry, altered range of motion (ROM), and tenderness according to DO-Touch.NET physical examination and treatment form. A literature review was conducted utilizing various search engines and the textbook, Stiehm's Immune Deficiencies, 4th edition. The significant findings found from the patient were right sidebending rotation cranial strain pattern with decreased left temporal bone motion, temporomandibular joint crepitus, and right deviation upon mandibular opening. The thoracolumbar region revealed tissue tenderness and restricted psoas ROM. Bilateral sacroiliac joint tenderness, right superior sheering, and anterior innominate rotation, along with left-on-left sacral flexion, were associated with valgus knees. The literature search showed multiple other PIDs outside of PIK3R1 that have associated skeletal and structural abnormalities. Irregular skeletal features found in immunodeficient patients may have an additive defect on the immunological responses due to somatic dysfunction impinging on the lymphatic flow to the central circulation. Other different immunodeficient patients suffer from boney structural abnormalities, which may lead to further immune hindrance caused by impingement of flow as well as bone marrow microenvironment impact on the peripheral immunological output. We present the first osteopathic examination with detailed findings of somatic dysfunction in a patient with PID. Future studies on PID patients should require more attention to structure and function, as found by a thorough osteopathic examination in order to unrestrict preformed cellular and humoral components back into the peripheral circulation.
