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New approach to investigate Common Variable Immunodeficiency patients using spectrochemical analysis of blood.

May 12, 2019 By Manish Butte

New approach to investigate Common Variable Immunodeficiency patients using spectrochemical analysis of blood.

Sci Rep. 2019 May 10;9(1):7239

Authors: Callery EL, Morais CLM, Paraskevaidi M, Brusic V, Vijayadurai P, Anantharachagan A, Martin FL, Rowbottom AW

Abstract
Common variable immune deficiency (CVID) is a primary immunodeficiency disease, characterized by hypogammaglobulinemia, recurrent infections and various complications. The clinical heterogeneity of CVID has hindered identification of an underlying immune defect; diagnosis relies on clinical judgement, alongside evidence-based criteria. The lack of pathognomonic clinical or laboratory features leads to average diagnostic delays of 5 years or more from the onset. Vibrational spectroscopic techniques such as Fourier-transform infrared (FTIR) spectroscopy have recently gained increasing clinical importance, being rapid-, non-invasive and inexpensive methods to obtain information on the content of biological samples. This has led us to apply FTIR spectroscopy to the investigation of blood samples from a cohort of CVID patients; revealing spectral features capable of stratifying CVID patients from healthy controls with sensitivities and specificities of 97% and 93%, respectively for serum, and 94% and 95%, respectively for plasma. Furthermore we identified several discriminating spectral biomarkers; wavenumbers in regions indicative of nucleic acids (984 cm-1, 1053 cm-1, 1084 cm-1, 1115 cm-1, 1528 cm-1, 1639 cm-1), and a collagen-associated biomarker (1528 cm-1), which may represent future candidate biomarkers and provide new knowledge on the aetiology of CVID. This proof-of-concept study provides a basis for developing a novel diagnostic tool for CVID.

PMID: 31076587 [PubMed – in process]

Impact of patient comorbidities on surgical site infection within 90 days of primary and revision joint (hip and knee) replacement.

May 11, 2019 By Manish Butte

Impact of patient comorbidities on surgical site infection within 90 days of primary and revision joint (hip and knee) replacement.

Am J Infect Control. 2019 May 06;:

Authors: Edmiston CE, Chitnis AS, Lerner J, Folly E, Holy CE, Leaper D

Abstract
BACKGROUND: The frequency of primary and revision total knee and hip replacements (pTKRs, rTKRs, pTHRs, and rTHRs, respectively) is increasing in the United States due to demographic changes. This study evaluated the impact of preoperative patient and clinical factors on the risk of surgical site infection (SSI) within the 90-day period after primary and revision total joint replacements (TJR).
METHODS: A retrospective observational cohort study was designed using the IBM MarketScan and Medicare databases, 2009-2015. Thirty-four comorbidities were assessed for all patients, and multivariable logistic regression models were used to evaluate factors associated with higher odds of SSI after adjusting for other patient and clinical preoperative conditions.
RESULTS: The study included a total of 335,134 TKRs and 163,547 THRs. SSI rates were 15.6% and 8.6% after rTKR and rTHR, respectively, compared with 2.1% and 2.1% for pTKR and pTHR, respectively. Comorbidities with the greatest adjusted effect on SSI across all TJRs were acquired immunodeficiency syndrome (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.06-2.34; P = .0232), paralysis (OR, 1.56; 95% CI, 1.26-1.94; P < .0001), coagulopathy (OR, 1.48; 95% CI, 1.36-1.62; P < .0001), metastatic cancer (1.48; 95% CI, 1.24-1.76; P < .0001), and congestive heart failure (OR, 1.39; 95% CI, 1.30-1.49; P < .0001).
CONCLUSIONS: SSI occurred most commonly among patients after revision TJR and were related to many patient comorbidities, including diabetes, congestive heart failure, and coagulopathy, which were significantly associated with a higher risk of SSI after TJR.

PMID: 31072674 [PubMed – as supplied by publisher]

“Noninfectious” Cutaneous Granulomas in Primary Immunodeficiency Patients and Association With Rubella Virus Vaccine Strain.

May 10, 2019 By Manish Butte

“Noninfectious” Cutaneous Granulomas in Primary Immunodeficiency Patients and Association With Rubella Virus Vaccine Strain.

J Cutan Med Surg. 2019 May/Jun;23(3):341-342

Authors: Murguia-Favela L, Hiebert J, Haber RM

PMID: 31070095 [PubMed – in process]

The utility of flow cytometry for the diagnosis of primary immunodeficiencies.

May 10, 2019 By Manish Butte

The utility of flow cytometry for the diagnosis of primary immunodeficiencies.

Int J Lab Hematol. 2019 May;41 Suppl 1:63-72

Authors: Knight V

Abstract
Primary immunodeficiencies (PID) or inborn errors of immunity affect phenotype and/or function of one or more components of the immune system. The exponential growth of genetic analysis has enabled identification of known and novel mutations. However, genetic analysis continues to be expensive and is not easily accessible. Flow cytometry, on the other hand, has been well established for many years in clinical laboratories and its use for the analysis of immunodeficiencies is expanding. Surface, intracellular, and intranuclear proteins can easily be evaluated by flow cytometry, enabling both phenotypic and functional identification of specific cell populations and therefore facilitating the identification of a variety of PIDs. While genetic analysis provides a definitive diagnosis for PIDs, flow cytometry is necessary to confirm or establish the immune phenotype of a gene mutation. Furthermore, flow cytometry provides a rapid means to identify an immunological defect at a relatively low cost.

PMID: 31069989 [PubMed – in process]

Familial Immune Thrombocytopenia Associated With a Novel Variant in IKZF1.

May 10, 2019 By Manish Butte

Familial Immune Thrombocytopenia Associated With a Novel Variant in IKZF1.

Front Pediatr. 2019;7:139

Authors: Sriaroon P, Chang Y, Ujhazi B, Csomos K, Joshi HR, Zhou Q, Close DW, Walter JE, Kumánovics A

Abstract
We report a novel variant in IKZF1 associated with IKAROS haploinsufficiency in a patient with familial immune thrombocytopenia (ITP). IKAROS, encoded by the IKZF1 gene, is a hematopoietic zinc-finger transcription factor that can directly bind to DNA. We show that the identified IKZF1 variant (p.His195Arg) alters a completely conserved histidine residue required for the folding of the third zinc-finger of IKAROS protein, leading to a loss of characteristic immunofluorescence nuclear staining pattern. In our case, genetic testing was essential for the diagnosis of IKAROS haploinsufficiency, of which known presentations include infections, aberrant hematopoiesis, leukemia, and age-related decrease in humoral immunity. Our family study underscores that, after infections, ITP is the second most common clinical manifestation of IKAROS haploinsufficiency.

PMID: 31069201 [PubMed]

A Novel Nonsense Mutation in FERMT3 Causes LAD-III in a Pakistani Family.

May 10, 2019 By Manish Butte

A Novel Nonsense Mutation in FERMT3 Causes LAD-III in a Pakistani Family.

Front Genet. 2019;10:360

Authors: Shahid S, Zaidi S, Ahmed S, Siddiqui S, Abid A, Malik S, Shamsi T

Abstract
Leukocyte adhesion deficiency-III (LAD3) is an extremely rare primary immunodeficiency disorder, transmitted with autosomal-recessive inheritance. It is caused by genetic alteration in the FERMT3 gene, which leads to abnormal expression of kindlin-3. This cytoplasmic protein is highly expressed in leukocytes and platelets, and acts as an important regulator of integrin activation. LAD3 has features like bleeding syndrome of Glanzmann-type and leukocyte adhesion deficiency. FERMT3 mutation(s) have not been well characterized in Pakistani patients with LAD3. In this study, an infant and his family of Pakistani origin, presenting with clinical features of LAD, were investigated to determine the underlying genetic defect. Targeted next generation sequencing (TGS) and Sanger sequencing were performed to identify and confirm the causative mutations, respectively, and their segregation within the family. A novel, homozygous FERMT3 nonsense mutation (c.286C > T, p.Q96∗) was found in the proband, and its co-segregation with LAD3 phenotype within the family was consistent with an autosomal recessive inheritance. Both parents were carriers of the same mutation. This family was offered prenatal diagnosis during first trimester of the subsequent pregnancy; the fetus carried the variant. In conclusion, our study is the first report to identify the novel homozygous variant c.286C > T, p.Q96∗in the FERMT3 gene, which might be the causative mutation for LAD3 patients of Pakistani origin.

PMID: 31068971 [PubMed]

[Cytopenia under topical imiquimod in two patients treated with oral hydroxyurea].

May 10, 2019 By Manish Butte

[Cytopenia under topical imiquimod in two patients treated with oral hydroxyurea].

Ann Dermatol Venereol. 2018 Dec;145(12):765-768

Authors: Joachim C, Gras-Champel V, Marolleau JP, Chaby G, Dairi M, Carmi E

Abstract
BACKGROUND: Aldara® is a topical immunomodulatory treatment. The risks of systemic passage are minimal. There have been rare reports of systemic adverse effects.
PATIENTS AND METHODS: Case 1. Five sachets weekly of imiquimod were prescribed for Bowen’s disease on the forearm in a patient known to have essential thrombocytosis under Hydrea®. His CBC was normal (6000 leukocytes/mm3, 2200 PMN/mm, 230,000 platelets/mm3). Imiquimod was given in 15 sachets weekly. Fifteen day later, the patient presented bicytopenia (3000 leukocytes/mm3, 1400 PMN/mm3, 119,000 platelets/mm3). Hydroxyurea and imiquimod were suspended until normalization of CBC. Hydroxyurea was resumed without recurrence of the bicytopenia. The patient’s history included an identical episode following application of imiquimod. Case 2. Five sachets weekly of imiquimod were prescribed for actinic keratosis on the scalp in a patient known to have primary polycythemia under hydroxyurea. Her CBC was normal except for anemia (Hb 11.5g/L, 160,000 platelets/mm3, 1100 lymphocytes/mm3). Imiquimod was given in 12 sachets weekly. Ten days later, anemia increased (Hb 10g/dL) with lymphopenia (800/mm3) and thrombocytopenia (115,000/mm3). Suspension of imiquimod resulted in normalization of the previous CBC values.
DISCUSSION: . The literature review identified reports of dose-dependent lymphopenia under oral imiquimod but not under Aldara®. The National Pharmacovigilance Database listed 10 cases of hematological disorders most likely caused by Aldara®. Hydroxyurea may induce cytopenia, and while it was not considered the sole causative agent in this case, it is likely to have had a triggering role in these patients with blood dyscrasias. Our findings show that misuse of imiquimod carries a potential risk of hematologic abnormality in patients receiving concomitant hydroxyurea, a commonly combined drug.

PMID: 30217687 [PubMed – indexed for MEDLINE]

A Rare Case of Hyper IgE Syndrome with Vocal Cords Involvement.

May 9, 2019 By Manish Butte

A Rare Case of Hyper IgE Syndrome with Vocal Cords Involvement.

Iran J Allergy Asthma Immunol. 2019 Apr 01;18(2):225-229

Authors: Sharafian S, Movahedi M, Kalantari A, Parvaneh N, Gharagozlou M

Abstract
Hyperimmunoglobulin E syndrome (HIGE) is considered as a phagocytic or a newly classified complex and heterogeneous primary immunodeficiency disease with symptoms such as increased levels of immunoglobulin E, eczema, and, recurrent lung and skin infections. In this paper, we have presented a rare case of this syndrome. A 9-year-old Iranian girl presented with a history of pruritic maculopapular rash who was eventually diagnosed as a case of HIGE. In her recent admission, she had dysphonia, stridor and huge cauliflower cutaneous lesions on her neck, finger and vocal cords, which did not respond to intravenous antibiotics, and ultimately required surgical removal.

PMID: 31066259 [PubMed – in process]

Determining Laboratory Reference Values of TREC and KREC in Different Age Groups of Iranian Healthy Individuals.

May 9, 2019 By Manish Butte

Determining Laboratory Reference Values of TREC and KREC in Different Age Groups of Iranian Healthy Individuals.

Iran J Allergy Asthma Immunol. 2019 Apr 01;18(2):143-152

Authors: Shakerian L, Pourpak Z, Shamlou S, Domsgen E, Kazemnejad A, Dalili H, Nourizadeh M

Abstract
Assessment of the number of T-cell receptor excision circles (TREC) and kappa-deleting recombination excision circles (KREC) copies has been recently described as biomarkers of newly formed T and B cells respectively. In this study, we aimed to explore the effects of demographic variables including age, gender, weight, height and ethnicity on these two episomal DNA molecules. Second, for the first time in our country, we determined the reference values of TREC and KREC copy numbers in different age groups of Iranian healthy individuals as a threshold for identifying T cell and B cell lymphopenia. The TREC and KREC copy numbers were evaluated in 251 dried blood spot (DBS) samples from healthy volunteers (age range: 0-60 years). Six primary immunodeficiency (PID) patients were included as disease controls. TREC and KREC copies were markedly reduced with increasing age. Although the levels of TREC and KREC were higher in females than males, this difference did not reach statistical significance. These findings suggest that demographic variables including age should be considered for interpretation results of the TREC/KREC assay.

PMID: 31066250 [PubMed – in process]

Recent Advances in Gene Therapy and Modeling of Chronic Granulomatous Disease.

May 9, 2019 By Manish Butte

Recent Advances in Gene Therapy and Modeling of Chronic Granulomatous Disease.

Iran J Allergy Asthma Immunol. 2019 Apr 01;18(2):131-142

Authors: Jafarian A, Shokri G, Shokrollahi Barough M, Moin M, Pourpak Z, Soleimani M

Abstract
The Chronic granulomatous disease (CGD) is a primary immunodeficiency that characterized by mutations in phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, resulting in deficient antimicrobial activity of phagocytic cells and recurrent childhood infections. Hematopoietic stem cell transplantation (HSCT) is a curative option for patients with human leukocyte antigen (HLA) matched donor, when conventional cares and therapies fail. However, in many cases when the patients have not an HLA-matched donor, they need to a method to recapitulate the function of the affected gene within the patient’s own cells. Gene therapy is a promising approach for CGD. While, the success of retroviral or lentiviral vectors in gene therapy for CGD has been hampered by random integration and insertional activation of proto-oncogenes. These serious adverse events led to improvement and generations of viral vectors with increased safety characteristics. Gene therapy continues to progress and the advent of new technologies, such as engineered endonucleases that have shown a great promise for the treatment of genetic disease. This review focuses on the application of gene therapy for the CGD, the limitations encountered in current clinical trials, advantages and disadvantages of endonucleases in gene correction and modeling with CRISPR/Cas9 approach.

PMID: 31066249 [PubMed – in process]