Beyond the skin: immunological profiles and infectious complications in
ALOX12B-associated autosomal recessive congenital ichthyosis
#MMPMID41346588
Sefer AP
; Catak MC
; An I
; Keser Ozturk N
; Baykal Selcuk L
; Dincer OS
; Benamar M
; Getachew F
; Schmitz-Abe K
; Agrawal PB
; Bayram Catak F
; Erman B
; Bilgic Eltan S
; Karakoc Aydiner E
; Ozen A
; Chatila T
; Baris S
Front Immunol
2025[]; 16
(?): 1662858
PMID41346588
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BACKGROUND: Pathogenic variants in ALOX12B, a crucial enzyme involved in
epidermal lipid processing, are among the most common causes of autosomal
recessive congenital ichthyosis (ARCI). Although traditionally considered a
cutaneous disorder, the systemic immunological implications of ALOX12B deficiency
remain poorly understood. OBJECTIVES: We aimed to broaden the dermatologic and
immunologic spectrum of ALOX12B-associated ARCI by characterizing the clinical,
immunologic, and genetic features of six patients from three consanguineous
families. METHODS: This prospective study included six patients with
ALOX12B-associated ARCI identified through whole-exome sequencing. Detailed
dermatological evaluations, infection histories, immunoglobulin profiles,
lymphocyte subset analyses, and vaccine response assessments were performed.
RESULTS: All patients exhibited early-onset generalized ichthyosis, ranging from
delayed-onset lamellar ichthyosis to collodion membrane presentations accompanied
by nonbullous erythroderma. Two distinct biallelic ALOX12B variants were
identified: a novel p.Thr383Lys and the known p.Cys544Arg. Several patients
demonstrated recurrent bacterial or fungal infections (n = 5), markedly elevated
serum IgE levels (n = 4), and isolated abnormalities in vaccine responsiveness (n
= 2). Lymphocyte counts and other immunoglobulin classes were generally
preserved; however, decreased IgG levels were observed in one patient (P3.1).
Intravenous immunoglobulin replacement therapy reduced the frequency of
infections in patients (P1.1 and P1.2). CONCLUSIONS: Our findings suggest that
ALOX12B-related ARCI may involve secondary immune dysregulation, driven by
chronic compromise of the epidermal barrier. An immunologic evaluation is
warranted in selected cases, particularly those with a history of susceptibility
to infections. Multidisciplinary care, encompassing dermatology, immunology, and
genetics, is crucial for achieving optimal outcomes in ARCI.
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