Adult-onset manifestation of idiopathic T-cell lymphopenia due to a heterozygous RAG1 mutation

Abraham, Roshini S.; Recher, Mike; Giliani, Silvia; Walter, Jolán E.; Lee, Yu Nee; Frugoni, Francesco; Maddox, Daniel E.; Kirmani, Salman; Notarangelo, Luigi D.

doi:10.1016/j.jaci.2012.09.016

Cited by 30 publications

(25 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The CID-G/AI phenotype is associated with unique clinical features resembling granulomatosis with polyangitis as well as complications of midline destruction or chronic sterile multi-focal osteomyelitis. Moreover, T cell lymphopenia without overt manifestations of autoimmunity has also been associated with pathogenic RAG mutations [18, 19]. …”

Section: Discussionmentioning

confidence: 99%

Identification of Patients with RAG Mutations Previously Diagnosed with Common Variable Immunodeficiency Disorders

et al. 2014

Self Cite

View full text Add to dashboard Cite

Purpose Combined immunodeficiency (CID) presents a unique challenge to clinicians. Two patients presented with the prior clinical diagnosis of common variable immunodeficiency (CVID) disorder marked by an early age of presentation, opportunistic infections, and persistent lymphopenia. Due to the presence of atypical clinical features, next generation sequencing was applied documenting RAG deficiency in both patients. Methods Two different genetic analysis techniques were applied in these patients including whole exome sequencing in one patient and the use of a gene panel designed to target genes known to cause primary immunodeficiency disorders (PIDD) in a second patient. Sanger dideoxy sequencing was used to confirm RAG1 mutations in both patients. Results Two young adults with a history of recurrent bacterial sinopulmonary infections, viral infections, and autoimmune disease as well as progressive hypogammaglobulinemia, abnormal antibody responses, lymphopenia and a prior diagnosis of CVID disorder were evaluated. Compound heterozygous mutations in RAG1 (1) c256_257delAA, p86VfsX32 and (2) c1835A>G, pH612R were documented in one patient. Compound heterozygous mutations in RAG1 (1) c.1566G>T, p.W522C and (2) c.2689C>T, p. R897X) were documented in a second patient post-mortem following a fatal opportunistic infection. Conclusion Astute clinical judgment in the evaluation of patients with PIDD is necessary. Atypical clinical findings such as early onset, granulomatous disease, or opportunistic infections should support the consideration of atypical forms of late onset CID secondary to RAG deficiency. Next generation sequencing approaches provide powerful tools in the investigation of these patients and may expedite definitive treatments.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of Patients with RAG Mutations Previously Diagnosed with Common Variable Immunodeficiency Disorders

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…Another patient with adult onset immunodefi ciency caused by heterozygote ADA defi ciency was reported by Shovlin et al [17]. Additional to these articles reported by Abraham et al [16] and Shovlin et al [17], Pico-Knijnenburg et al [18] reported three siblings who had recurrent infections, generalized rashes, malnutrition and chronic diarrhoea. In those siblings, there were extremely low T and B cells.…”

Section: Discussionmentioning

confidence: 94%

“…OS presents erythroderma, eosinophilia, lymphadenopathy, and increased serum IgE levels as presented in patient #3. In medical literature, it has been reported two adult onset immunodefi ciency caused by heterozygous mutations in RAG1 and adenosine deaminase defi ciency (ADA) [16][17] as in patient #3. Abraham et al [16] reported a patient presented with chronic dermatitis, pruritus, and hyperkeratosis.…”

Section: Discussionmentioning

confidence: 99%

“…In medical literature, it has been reported two adult onset immunodefi ciency caused by heterozygous mutations in RAG1 and adenosine deaminase defi ciency (ADA) [16][17] as in patient #3. Abraham et al [16] reported a patient presented with chronic dermatitis, pruritus, and hyperkeratosis. In that patient, the clinical and immunologic examination showed eosinophilia, elevated IgE (747 kU/L), profound pan-T-cell lymphopenia results from heterozygous RAG1 mutation as in our patient #3.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Three faces of recombination activating gene 1 (RAG1) mutations

Patıroğlu

Akar

Burg

2015

Acta Microbiologica et Immunologica Hungarica

View full text Add to dashboard Cite

Severe combined immune defi ciency (SCID) is a group of genetic disorder associated with development of T-and/or B-lymphocytes. Recombination-activating genes (RAG1/2) play a critical role on VDJ recombination process that leads to the production of a broad T-cell receptor (TCR) and B-cell receptor (BCR) repertoire in the development of T and B cells. RAG1/2 genes mutations result in various forms of primary immunodefi ciency, ranging from classic SCID to Omenn syndrome (OS) to atypical SCID with such as granuloma formation and autoimmunity. Herein, we reported 4 patients with RAG1 defi ciency: classic SCID was seen in two patients who presented with recurrent pneumonia and chronic diarrhoea, and failure to thrive. OS was observed in one patient who presented with chronic diarrhoea, skin rash, recurrent lower respiratory infections, and atypical SCID was seen in one patient who presented with Pyoderma gangrenosum (PG) and had novel RAG1 mutation.

show abstract

“…11 Genetic etiologies have not been identified in most, although in a few outliers, lymphocyte-specific kinase, uncoordinated 119, IL-2–inducible T-cell kinase deficiency, and heterozygous RAG1 have been reported as causative in a few rare patients. 14–19 …”

Section: Discussionmentioning

confidence: 99%

Idiopathic CD4 lymphocytopenia

Yarmohammadi

Cunningham‐Rundles

2017

Annals of Allergy, Asthma & Immunology

View full text Add to dashboard Cite

Background Idiopathic CD4 lymphocytopenia (ICL) is a rare condition characterized by an unexplained deficit of circulating CD4 T cells leading to increased risk of serious opportunistic infections. The pathogenesis, etiology, clinical presentation, and best treatment options remain unclear. Objective To describe the clinical presentation, treatment strategies, and outcome of patients with ICL seen in a single referral center. Methods In a retrospective study, from January 1993 to January 2014, the demographic characteristics, clinical presentation, and treatments of patients diagnosed with ICL were reviewed. Results Twenty-four patients (14 female [58%] and 10 male [42%]) were evaluated. The mean age was 45 ± 17.6 years (range 7–76 years). Mean CD4 and CD8 T-cell counts at the time of diagnosis were 119 ± 84/mm3 (range 4–294/mm3) and 219 ± 258/mm3 (range 7–630/mm3), respectively. Seventeen patients (71%) had opportunistic infections, 4 (17%) had malignancies, and 3 (13%) had unexplained demyelinating disease and neurologic problems. Most patients had normal levels of immunoglobulins. Thirteen patients had abnormally low to absent response to phytohemagglutinin, concanavalin A, and antigens (candida and tetanus). Three patients had resolution of warts and 1 had mycobacterial lung infection on interleukin-2 with increases in CD4 count. The 11 patients on trimethoprim and sulfamethoxazole had no further hospital admissions for infections. Conclusion The pathogenesis of ICL remains unclear. Although only some patients are healthy, most patients present with opportunistic infections. There is no known standard treatment aside from prophylactic antibiotics.

show abstract

Adult-onset manifestation of idiopathic T-cell lymphopenia due to a heterozygous RAG1 mutation

Cited by 30 publications

References 7 publications

Identification of Patients with RAG Mutations Previously Diagnosed with Common Variable Immunodeficiency Disorders

Identification of Patients with RAG Mutations Previously Diagnosed with Common Variable Immunodeficiency Disorders

Three faces of recombination activating gene 1 (RAG1) mutations

Idiopathic CD4 lymphocytopenia

Contact Info

Product

Resources

About