There are three major categories of antibody deficiencies: (a) defects in early B cell development, (b) hyper-IgM syndromes (also called class switch recombination defects), and (c) common variable immunodeficiency (CVID). Category (b), hyper-IgM syndrome (HIM), represents a group of distinct entities characterized by defective normal or elevated IgM in the presence of diminished IgG and IgA levels. Seventy per cent of the cases are X-linked in inheritance, and others are autosomal recessive. In the autosomal recessive hyper IgM syndromes, the problem lies in the nucleotide-editing enzymes AICD or UNG. These enzymes are only present in the germinal center B cells, and defects in either disrupt B-cell development and antibody production. Patients with these syndromes typically have recurrent bacterial infections and often have lymphoid hyperplasia.
Category
Immune system disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
04 Diseases of the immune system
Primary immunodeficiencies
4A01 Primary immunodeficiencies due to disorders of adaptive immunity
H00086 Immunodeficiency with hyper-IgM
Pathway-based classification of diseases [BR:br08402]
Replication and repair
nt06504 Base excision repair
H00086 Immunodeficiency with hyper-IgM
Signal transduction
nt06516 TNF signaling
H00086 Immunodeficiency with hyper-IgM
Revy P, Muto T, Levy Y, Geissmann F, Plebani A, Sanal O, Catalan N, Forveille M, Dufourcq-Labelouse R, Gennery A, Tezcan I, Ersoy F, Kayserili H, Ugazio AG, Brousse N, Muramatsu M, Notarangelo LD, Kinoshita K, Honjo T, Fischer A, Durandy A
Title
Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2).
Bare lymphocyte syndrome type 1 [DS:H00984] Bare lymphocyte syndrome type 2 [DS:H00985] Immunodeficiency with hyper-IgM [DS:H00086] Combined cellular and humoral deficiencies and multiple granulomas (CCHDG)
Supergrp
Disorders of adaptive immunity [DS:H02526] Primary immunodeficiency disease [DS:H01725]
Description
The term combined immunodeficiency (CID) is used to distinguish patients with low, but not absent, T-cell function from those with severe CID (SCID) characterized by profound deficiencies of T- and B-cell (and sometimes NK- cell) function. Hyper-IgM syndrome (HIM) [DS:H00086] represents a group of distinct entities characterized by defective normal or elevated IgM in the presence of diminished IgG and IgA levels. The genetic anomaly in X-linked hyper-IgM syndrome has been mapped to Xq26, and resides in mutations of the CD40 ligand gene. ZAP-70 deficiency is inherited in an autosomal recessive manner. Recurrent and opportunistic infections occur within the first year of life. The mutations in genes responsible for CRAC channel function, ORAI1 and STIM1, cause the defect in Ca2+ influx.
Category
Primary immunodeficiency
Brite
Human diseases in ICD-11 classification [BR:br08403]
04 Diseases of the immune system
Primary immunodeficiencies
4A01 Primary immunodeficiencies due to disorders of adaptive immunity
H00093 Combined immunodeficiency
Pathway-based classification of diseases [BR:br08402]
Replication and repair
nt06509 DNA replication
H00093 Combined immunodeficiency
Signal transduction
nt06530 PI3K signaling
H00093 Combined immunodeficiency
nt06518 JAK-STAT signaling
H00093 Combined immunodeficiency
nt06516 TNF signaling
H00093 Combined immunodeficiency
nt06528 Calcium signaling
H00093 Combined immunodeficiency
Immune system
nt06537 TCR/BCR signaling
H00093 Combined immunodeficiency
Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee.
Stepensky P, Keller B, Buchta M, Kienzler AK, Elpeleg O, Somech R, Cohen S, Shachar I, Miosge LA, Schlesier M, Fuchs I, Enders A, Eibel H, Grimbacher B, Warnatz K
Title
Deficiency of caspase recruitment domain family, member 11 (CARD11), causes profound combined immunodeficiency in human subjects.
Cardinez C, Miraghazadeh B, Tanita K, da Silva E, Hoshino A, Okada S, Chand R, Asano T, Tsumura M, Yoshida K, Ohnishi H, Kato Z, Yamazaki M, Okuno Y, Miyano S, Kojima S, Ogawa S, Andrews TD, Field MA, Burgio G, Morio T, Vinuesa CG, Kanegane H, Cook MC
Title
Gain-of-function IKBKB mutation causes human combined immune deficiency.
Hauck F, Randriamampita C, Martin E, Gerart S, Lambert N, Lim A, Soulier J, Maciorowski Z, Touzot F, Moshous D, Quartier P, Heritier S, Blanche S, Rieux-Laucat F, Brousse N, Callebaut I, Veillette A, Hivroz C, Fischer A, Latour S, Picard C
Title
Primary T-cell immunodeficiency with immunodysregulation caused by autosomal recessive LCK deficiency.
Martin E, Palmic N, Sanquer S, Lenoir C, Hauck F, Mongellaz C, Fabrega S, Nitschke P, Esposti MD, Schwartzentruber J, Taylor N, Majewski J, Jabado N, Wynn RF, Picard C, Fischer A, Arkwright PD, Latour S
Title
CTP synthase 1 deficiency in humans reveals its central role in lymphocyte proliferation.
Torres JM, Martinez-Barricarte R, Garcia-Gomez S, Mazariegos MS, Itan Y, Boisson B, Rholvarez R, Jimenez-Reinoso A, del Pino L, Rodriguez-Pena R, Ferreira A, Hernandez-Jimenez E, Toledano V, Cubillos-Zapata C, Diaz-Almiron M, Lopez-Collazo E, Unzueta-Roch JL, Sanchez-Ramon S, Regueiro JR, Lopez-Granados E, Casanova JL, Perez de Diego R
Title
Inherited BCL10 deficiency impairs hematopoietic and nonhematopoietic immunity.
Lagresle-Peyrou C, Luce S, Ouchani F, Soheili TS, Sadek H, Chouteau M, Durand A, Pic I, Majewski J, Brouzes C, Lambert N, Bohineust A, Verhoeyen E, Cosset FL, Magerus-Chatinet A, Rieux-Laucat F, Gandemer V, Monnier D, Heijmans C, van Gijn M, Dalm VA, Mahlaoui N, Stephan JL, Picard C, Durandy A, Kracker S, Hivroz C, Jabado N, de Saint Basile G, Fischer A, Cavazzana M, Andre-Schmutz I
Title
X-linked primary immunodeficiency associated with hemizygous mutations in the moesin (MSN) gene.
Haapaniemi EM, Fogarty CL, Keskitalo S, Katayama S, Vihinen H, Ilander M, Mustjoki S, Krjutskov K, Lehto M, Hautala T, Eriksson O, Jokitalo E, Velagapudi V, Varjosalo M, Seppanen M, Kere J
Title
Combined immunodeficiency and hypoglycemia associated with mutations in hypoxia upregulated 1.
Thian M, Hoeger B, Kamnev A, Poyer F, Kostel Bal S, Caldera M, Jimenez-Heredia R, Huemer J, Pickl WF, Gross M, Ehl S, Lucas CL, Menche J, Hutter C, Attarbaschi A, Dupre L, Boztug K
Title
Germline biallelic PIK3CG mutations in a multifaceted immunodeficiency with immune dysregulation.
Roussel L, Landekic M, Golizeh M, Gavino C, Zhong MC, Chen J, Faubert D, Blanchet-Cohen A, Dansereau L, Parent MA, Marin S, Luo J, Le C, Ford BR, Langelier M, King IL, Divangahi M, Foulkes WD, Veillette A, Vinh DC
Title
Loss of human ICOSL results in combined immunodeficiency.
Conde CD, Petronczki OY, Baris S, Willmann KL, Girardi E, Salzer E, Weitzer S, Ardy RC, Krolo A, Ijspeert H, Kiykim A, Karakoc-Aydiner E, Forster-Waldl E, Kager L, Pickl WF, Superti-Furga G, Martinez J, Loizou JI, Ozen A, van der Burg M, Boztug K
Title
Polymerase delta deficiency causes syndromic immunodeficiency with replicative stress.
Bravo Garcia-Morato M, Aracil Santos FJ, Briones AC, Blazquez Moreno A, Del Pozo Mate A, Dominguez-Soto A, Beato Merino MJ, Del Pino Molina L, Torres Canizales J, Marin AV, Vallespin Garcia E, Feito Rodriguez M, Plaza Lopez Sabando D, Jimenez-Reinoso A, Mozo Del Castillo Y, Sanz Santaeufemia FJ, de Lucas-Laguna R, Cardenas PP, Casamayor Polo L, Coronel Diaz M, Vales-Gomez M, Roldan Santiago E, Ferreira Cerdan A, Nevado Blanco J, Corbi AL, Reyburn HT, Regueiro JR, Lopez-Granados E, Rodriguez Pena R
Title
New human combined immunodeficiency caused by interferon regulatory factor 4 (IRF4) deficiency inherited by uniparental isodisomy.
De Ravin SS, Cowen EW, Zarember KA, Whiting-Theobald NL, Kuhns DB, Sandler NG, Douek DC, Pittaluga S, Poliani PL, Lee YN, Notarangelo LD, Wang L, Alt FW, Kang EM, Milner JD, Niemela JE, Fontana-Penn M, Sinal SH, Malech HL
Title
Hypomorphic Rag mutations can cause destructive midline granulomatous disease.
