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APDS Cohorts and Cases

Angulo I, et al. Science. 2013;342(6160):866-871. With Lucas, one of the two studies first discovering APDS (specifically APDS1).

Coulter TI, et al. J Allergy Clin Immunol. 2017;139(2):597-606.e4. A description of the clinical manifestations, laboratory findings, and treatments of a large cohort of patients with APDS1 (n=53).

Deau MC, et al. J Clin Invest. 2014;124(9):3923-3928. With Lucas, one of the two studies first describing APDS2.

Elkaim E, et al. J Allergy Clin Immunol. 2016;138(1):210-218.e9. A description of the clinical manifestations, laboratory findings, and treatments of the largest cohort of patients with APDS2 (n=36).

Jamee M, et al. Clin Rev Allergy Immunol. 2020;59(3):323-333. A systematic review of the clinical manifestations and laboratory findings of patients with APDS (n=243). Also includes analysis comparing features of APDS1 and APDS2, identifies the most common initial manifestations and incorrect diagnoses, and calculates median ages of symptom onset.

Lucas CL, et al. Nat Immunol. 2014;15(1):88-97. With Angulo, one of the two studies first discovering APDS (specifically APDS1).

Lucas CL, et al. J Exp Med. 2014;211(13):2537-2547. With Deau, one of the two studies first describing APDS2.

Maccari ME, et al. Front Immunol. 2018;9:543. A large cohort of patients with APDS1 and APDS2 from the European Society for Immunodeficiencies (ESID) registry (n=68) describing the temporal evolution of clinical manifestations and laboratory findings. It also discusses management, and provides an in-depth study of sirolimus (rapamycin) treatment (n=26).

Oh J, et al. J Allergy Clin Immunol Pract. 2021;S2213-2198(21)00885-0. A cohort of 40 APDS patients from the USIDNET registry.

APDS Review Articles

Condliffe AM, Chandra A. Front Immunol. 2018;9:338. A description of how infection and lymphoproliferation may both contribute to bronchiectasis and other respiratory manifestations in APDS.

Lucas CL, et al. Nat Rev Immunol. 2016;16(11):702-714. A review of the role of PI3K delta in T and B cells, as well as the clinical phenotypes of APDS.

Michalovich D, Nejentsev S. Front Immunol. 2018;9:369. An overview of the mutations causing APDS, clinical and immunological manifestations, and current and future treatment strategies.

Nunes-Santos CJ, Uzel G, Rosenzweig SD. J Allergy Clin Immunol. 2019;143(5):1676-1687. A comprehensive review of the APDS phenotype and mechanism of disease, including a discussion of combined immunodeficiency and immune dysregulation. It also describes the current treatment landscape.

Pham MN, Cunningham-Rundles C. Front Pediatr. 2018;6:402. A case reported followed by a discussion of lymphoproliferation and lymphoma in patients with APDS. Treatment options are also described in a convenient table.

Singh A, et al. Genes Dis. 2019;7(1):67-74. A review of APDS pathogenesis, genetics, clinical manifestations, and treatment.

Tangye SG, et al. J Clin Immunol. 2019;39(2):148-158. An emphasis of the importance of balanced PI3K delta signal for proper immune function before a description of the clinical phenotypes of APDS and its opposite, PI3K delta insufficiency.

Genetic Testing and APDS

Chinen J, et al. Ann Allergy Asthma Immunol. 2019;123(5):433-439. A practical approach to the available methodologies for identifying pathological genetic variants in patients with suspected primary immunodeficiency.

Chinn IK, et al. J Allergy Clin Immunol. 2020;145(1):46-69. A report from AAAAI on how to interpret genetic tests to diagnose patients with primary immunodeficiencies.

Heimall JR, et al. J Clin Immunol. 2018;38(3):320-329. Recommendations from CIS for the use of genetic testing for patients with primary immunodeficiencies, as well as a review of the types, strengths, and limitations of different genetic testing methods.

Quinn J, et al. Immunol Res. 2020;68(3):126-134. Outcomes of the Jeffrey Modell Foundation free global genetic sequencing pilot partnership with Invitae to identify specific primary immunodeficiency defects in order to optimize disease management and treatment.

General Primary Immunodeficiency and APDS

Bogaert DJ, et al. J Med Genet. 2016;53(9):575-590. A discussion of CVID as an umbrella diagnosis that may hide distinct monogenetic disease entities, such as APDS.

Bousfiha A, et al. J Clin Immunol. 2020;40(1):66-81. 2019 update to the IUIS primary immunodeficiency (inborn errors of immunity) phenotypic classification of 430 single-gene diseases.

Hartog NL, Williams KW, Abraham RS. Front Immunol. 2019;10:1783. A review of patient-centric care for primary immunodeficiencies from US and global perspectives.

Modell V, et al. Immunol Res. 2017;65(3):713-720. An analysis of strategies for identifying patients with primary immunodeficiencies, including Jeffrey Modell Foundation’s 10 Warning Signs, the 4 Stages of Testing Algorithm, physician-reported clinical outcomes, programs of physician education and public awareness, the SPIRIT® Analyzer, and newborn screening. It also highlights how diagnosis can improve patient outcomes and reduce costs.

Tangye SG, et al. J Clin Immunol. 2020;40(1):24-64. 2019 update to the IUIS primary immunodeficiency (inborn errors of immunity) phenotypic classification of 430 single-gene diseases.

Walter JE, et al. J Allergy Clin Immunol Pract. 2016;4(6):1089-1100. Strategies for managing the autoimmune and inflammatory aspects of primary immunodeficiencies.

Lymphoma and APDS

Crank MC, et al. J Clin Immunol. 2014;34(3):272-276. A case series (n=3) describing increased risk of malignancy in patients with APDS.

Kracker S, et al. J Allergy Clin Immunol. 2014;134(1):233-236. A case series (n=2) describing increased susceptibility of patients with APDS to B cell lymphomas.

Mayor PC, et al. J Allergy Clin Immunol. 2018;141(3):1028-1035. An analysis showing an increased incidence of cancer, particularly lymphoma, in patients with primary immunodeficiencies.

Shapiro RS. Am J Hematol. 2011;86(1):48-55. A review for hematologists/oncologists describing the implications of malignancies in the setting of primary immunodeficiencies.

Hematology and Primary Immunodeficiency Overlap in APDS

Chandrakasan S, et al. Pediatr Blood Cancer. 2019 May;66(5):e27619.  Clinical pearls and pitfalls in diagnosing an array of lymphoproliferative disorders and lymphoma. Differential diagnoses for these which include primary immunodeficies are illustrated through case studies.

Feuille EJ, et al. J Clin Immunol. 2018;38(1):28-34. An analysis demonstrating the prevalence of autoimmune cytopenias in CVID and their association with non-infectious complications that may be seen by non-immunologists, highlighting the need for other specialties to be aware of primary immunodeficiencies.

Rotz SJ, Ware RE, Kumar A. Pediatr Blood Cancer. 2018;65(10):e27260. A review for hematologists explaining the diagnostic workup for chronic and refractory autoimmune cytopenias in children, adolescents, and young adults. It highlights when genetic testing may be warranted and includes APDS in the differential diagnosis.

Sánchez-Ramón S, et al. Front. Immunol. 2019;10:586. Physician consensus paper on when to include pirmary immunodeficiencies (PI) in hematological differential diagnoses. Diagnostic workup is given for PIs.

Management of APDS

Coulter TI, Cant AJ. Front Immunol. 2018;9:2043. A review of the treatment options available for patients with APDS.

Dimitrova D, et al. J Allergy Clin Immunol. 2021;S0091-6749(21)00810-1. The largest study of hematopoietic stem cell transplant for patients with APDS (n=57), demonstrating the severe complications that can occur for some patients.

Kang JM, et al. Yonsei Med J. 2020;61(6):542-546. A case series (n=3) of Korean patients with APDS1 and their treatment with sirolimus (rapamycin).

Nademi Z, et al. J Allergy Clin Immunol. 2017;139(3):1046-1049. The first series of hematopoietic stem cell transplant in patients with APDS (n=11).

Okano T, et al. J Allergy Clin Immunol. 2019;143(1):266-275. A Japanese cohort of patients with APDS1 undergoing hematopoietic stem cell transplant (n=9), highlighting the benefits and complications of the procedure.

Rao VK, et al. Blood. 2017;130(21):2307-2316. A phase 2 trial of the PI3K delta inhibitor leniolisib in patients with APDS (n=6) demonstrating safety and efficacy.

Gastroenterology and APDS

Agarwal S, Cunningham-Rundles C. Immunol Allergy Clin North Am. 2019;39(1):81-94. A review of the gastrointestinal manifestations of primary immunodeficiencies, highlighting that these may be the first manifestation and that poor response to treatment should prompt immune evaluation.

Lindoso L, et al. Am J Gastroenterol. 2019;114:S14. A case series (n=3) demonstrating that patients with APDS may present first to gastroenterologists with inflammatory bowel disease.

APD-US-2021-0028

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