TACI Mutations in Primary Antibody Deficiencies: A Nationwide Study in Greece
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients Characteristics
2.2. Molecular Analysis
2.3. Statistical Analysis
3. Results
3.1. Prevalence of TACI Mutations in the Patients of the Study
3.2. Associations of TACI Defects with Clinical Manifestations of the Patients of the Study
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Total | CVID | Combined IgAD & IgGsD | |
---|---|---|---|
No | 117 | 110 | 7 |
Sex (male/female) | 53/64 | 48/62 | 5/2 |
Age at analysis (mean ± SD) | 44.1 ± 15.9 | 44.8 ± 15.7 | 32.0 ± 13.9 |
Age at diagnosis (mean ± SD) | 36.0 ± 15.6 | 36.4 ± 15.6 | 28.4 ± 14.2 |
Age at disease onset (mean ± SD) | 24.7 ± 15.4 | 25.6 ± 15.3 | 11.1 ± 10.7 |
Lymphoproliferation (no, %) | 70 (59.8) | 67 (60.1) | 3 (42.9) |
Splenomegaly (no, %) | 60 (51.3) | 57 (51.2) | 3 (42.9) |
Lymphadenopathy (no, %) | 47 (40.2) | 45 (40.9) | 2 (28.6) |
Intestine infiltrates (no, %) | 10 (8.5) | 9 (8.2) | 1 (14.3) |
Hepatomegaly (no, %) | 26 (22.2) | 25 (25.0) | 1 (14.3) |
Infections (no, %) | 109 (93.2) | 102 (92.7) | 7 (100.0) |
Upper respiratory (no, %) | 98 (83.8) | 92 (83.6) | 6 (85.7) |
Lower respiratory (no, %) | 73 (62.4) | 70 (63.6) | 3 (42.9) |
Gastrointestinal (no, %) | 28 (23.9) | 27 (24.5) | 1 (14.3) |
Urinary (no, %) | 29 (24.8) | 29 (26.4) | 0 (0) |
Others ^ (no, %) | 27 (23.1) | 27 (24.5) | 0 (0) |
Bronchiectasis (no, %) | 27 (23.1) | 26 (23.6) | 1 (14.3) |
Granulomatous disease (no, %) | 11 (9.4) | 10 (9.1) | 1 (14.3) |
Autoimmune manifestations (no, %) | 67 (57.3) | 61 (55.5) | 6 (85.7) |
Thyroid disease (no, %) | 27 (23.1) | 24 (21.8) | 3 (42.9) |
AHA and/or ATP and/or Evans syndrome (no, %) | 29 (24.8) | 26 (23.6) | 3 (42.9) |
Others # (no, %) | 25 (21.4) | 22 (20.0) | 3 (42.9) |
Atopy (no, %) | 34 (29.1) | 33 (30.0) | 1 (14.3) |
Splenectomy (no, %) | 13 (11.1) | 13 (11.8) | 0 (0) |
Adenoidectomy (no, %) | 9 (7.7) | 7 (6.4) | 2 (28.6) |
Tonsillectomy (no, %) | 16 (13.7) | 13 (11.8) | 3 (42.3) |
Neoplasia (no, %) | 22 (18.8) | 22 (20.0) | 0 (0) |
Other complications * (no, %) | 10 (8.5) | 10 (9.1) | 0 (0) |
Under replacement treatment (no, %) | 105 (89.7) | 100 (90.9) | 5 (71.4) |
TACI defects | ||||
---|---|---|---|---|
Total | No | Yes | ||
117 pts | 100 pts | 17 pts | ||
No (%) | No (%) | No (%) | p | |
A. CVID causative/modifier mutations | ||||
Homozygous | 0 (0.0) | 0 (0.0) | ||
Combined heterozygous | 4 (3.4) | 4 (23.5) | ||
Heterozygous | 13 (11.1) | 13 (76.5) | ||
rs34557412(p.C104R) | 10 (8.5) | 10 (58.8) | ||
rs72553883 (p.A181E) | 2 (1.7) | 2 (11.8) | ||
rs200013015 (R20C) | 1 (0.9) | 1 (5.9) | ||
rs1410473109 (C62Y) | 1 (0.9) | 1 (5.9) | ||
rs72553877 (p.I87N) | 4 (3.4) | 4 (23.5) | ||
rs200037919 (p.P151L) | 1 (0.9) | 1 (5.9) | ||
rs74811083 (p.K188M) | 1 (0.9) | 1 (5.9) | ||
rs201021960 (p.E236X) | 1 (0.9) | 1 (5.9) | ||
B. TACI exonic and intronic polymorphisms (No, allele frequencies %) | ||||
rs8072293 (p.T27=) | 161, 68.8 | 135, 67.5 | 26, 76.5 | 0.325 |
rs35062843 (p.97P=) | 10, 4.3 | 10, 5.0 | 0, 0.0 | 0.365 |
rs56063729 (p.V220A) | 7, 3.0 | 7, 3.5 | 0, 0.0 | 0.573 |
rs11078355 (p.S277=) | 96, 41.0 | 88, 44.0 | 8, 23.5 | 0.039 |
rs34562254 (p.P251L) | 25, 10.7 | 23, 11.5 | 2, 5.9 | 0.496 |
rs2274892 (g.24625A>C) | 101, 43.2 | 91, 45.5 | 10, 29.4 | 0.118 |
rs11652843 (g.33402T>G) | 74, 31.6 | 67, 33.5 | 7, 20.6 | 0.194 |
rs11652811 (g.33482T>C) | 74, 31.6 | 67, 33.5 | 7, 20.6 | 0.194 |
Clinical Characteristics | TACI Molecular Defects | ||
---|---|---|---|
No | Yes | p | |
100 pts | 17 pts | ||
No (%) | No (%) | ||
Diagnosis | 0.593 | ||
CVID | 95 (86.4) | 15 (13.6) | |
Combined IgAD and IgGsD | 5 (71.4) | 2 (28.6) | |
Sex | 0.011 | ||
Male | 40 (75.5) | 13 (24.5) | |
Female | 60 (93.7) | 4 (6.3) | |
Age of disease onset, mean (SD) | 25.2 (15.5) | 21.9 (15.1) | 0.429 |
Age at diagnosis, mean (SD) | 36.4 (15.4) | 33.4 (17.1) | 0.460 |
Lymphoproliferation | 54 (54.0) | 16 (94.1) | 0.004 |
Splenomegaly | 47 (47.0) | 13 (76.5) | 0.047 |
Lymphadenopathy | 34 (34.0) | 13 (76.5) | 0.002 |
Intestine lymph infiltrates | 9 (9.0) | 1 (5.9) | 0.670 |
Hepatomegaly | 21 (21.0) | 5 (29.1) | 0.649 |
Infections | 93 (93.0) | 16 (94.1) | 0.866 |
Bronchiectasis | 25 (25.0) | 2 (11.8) | 0.376 |
Granulomatous disease | 10 (10.0) | 1 (5.9) | 0.929 |
Autoimmune manifestations | 56 (56.0) | 11 (64.7) | 0.685 |
Thyroid disease | 25 (25.0) | 2 (11.7) | 0.376 |
AHA and/or ATP and/or Evans syndrome | 21 (21.0) | 8 (47.1) | 0.046 |
Others * | 21 (21.0) | 4 (23.5) | 0.814 |
Atopy | 28 (28.0) | 6 (35.3) | 0.746 |
Splenectomy | 10 (10.0) | 3 (17.6) | 0.610 |
Adenoidectomy | 5 (5.0) | 4 (23.5) | 0.031 |
Tonsillectomy | 10 (10.0) | 6 (35.3) | 0.015 |
Neoplasia | 19 (19.0) | 3 (17.6) | 0.895 |
Other complications | 8 (8.0) | 2 (11.7) | 0.965 |
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Kakkas, I.; Tsinti, G.; Kalala, F.; Farmaki, E.; Kourakli, A.; Kapousouzi, A.; Dimou, M.; Kalaitzidou, V.; Sevdali, E.; Peristeri, A.-M.; et al. TACI Mutations in Primary Antibody Deficiencies: A Nationwide Study in Greece. Medicina 2021, 57, 827. https://doi.org/10.3390/medicina57080827
Kakkas I, Tsinti G, Kalala F, Farmaki E, Kourakli A, Kapousouzi A, Dimou M, Kalaitzidou V, Sevdali E, Peristeri A-M, et al. TACI Mutations in Primary Antibody Deficiencies: A Nationwide Study in Greece. Medicina. 2021; 57(8):827. https://doi.org/10.3390/medicina57080827
Chicago/Turabian StyleKakkas, Ioannis, Gerasimina Tsinti, Fani Kalala, Evangelia Farmaki, Alexandra Kourakli, Androniki Kapousouzi, Maria Dimou, Vassiliki Kalaitzidou, Eirini Sevdali, Athanasia-Marina Peristeri, and et al. 2021. "TACI Mutations in Primary Antibody Deficiencies: A Nationwide Study in Greece" Medicina 57, no. 8: 827. https://doi.org/10.3390/medicina57080827