Natural Killercell Deficiency (NKD)

    

    

    Figure 1: Different mutations of NKD.
    

Case Presentation

Two years old female child, third baby of their parents, resident of Multan (Punjab) visited Immunology Department, Armed Forces Institute of Pathology (AFIP) Rawalpindi. The child presented with H/O of recurrent episodes of fever and chest infections since the age of 7 months. Umbilical cord separation occurred on 6^th postnatal day. No history of abscesses, skin rash, diarrhea or mouth ulcers and she lost 3 kg weight in last one year. Child had poor response to antibiotics and received all vaccines till date. Her parents are first cousins. This patient have two elder sisters, both are healthy and achieved normal milestones on time. Her 3 maternal uncles were also healthy with no significant medical history. On examination, she looked malnourished with stable vitals, mild pallor, no cyanosis, mouth and skin ulcers. Liver and spleen were not palpable. The child was referred to AFIP Rawalpindi Immunology Department for Primary Immunodeficiency workup. Previous reports of this patient showed low Hb-8.8 g/dl with increase MCV, TLC 6.4x10⁹/L (70% lymphocytes) and Platelets 84x10⁹/L. Due to repeated lymphocytosis on complete blood counts, bone marrow aspiration was also performed which showed hypercellualr fragments, megakaryocytes but no blast cells were observed. For his decrease Hb, increase MCV and megakaryocytes presence in bone marrow, vitB12 and folic acid levels were performed which were found low. Serum ferritin was within upper limits of normal. Her serum Immunoglobulin level showed IgA 0.74 g/l (0.4-3.5), IgM 1.01 g/l (0.5-3), IgG8.77 g/l (6.5- 15) and IgE less than 150 IU/ml which was normal. HIV serology repeated twice on different occasions and was found negative. HRCT chest showed mild peribronchial wall thickening with no exudative lesion, lymphadenopathy or pleural fluid. Cystic fibrosis was also ruled out by sweat chloride test and F506 mutation analysis. Her lymphocytes counts showed normal T and B cells with very low number of NK cells that is 36 (normal range 300-600). After thorough history and considering the previous lab reports, following lab investigations were carried out at AFIP Rawalpindi including IgG subclasses, physiological antibodies response and lymphocyte subset analysis which showed IgG1 5.14 g/l (3.2-10.2), IgG2 1.14 g/l (1.2-6.6), IgG3 2.04 g/l (0.2-1.9), IgG4 0.15 g/l (0.1-1.5), Anti E coli and candida response was present and lymphocyte subset analysis showed absent NK cells with normal T and B cells population (Figure 2). To further confirm the diagnosis, viral antibodies profile was carried out at AFIP Rawalpindi which showed high titre of IgG antibodies, positive for Herpes simplex, varicella zoster, CMV and both IgM & IgG antibodies positive for EBV. On the basis of history, physical examination and lab investigations carried out at AFIP, final diagnosis of Natural Killer Cell Deficiency (NKD) was established. The functional NK cell assay not performed as NK cells were completely deficient and molecular diagnostic facility is not available in Pakistan. The patient parents were counseled and advised for viral prophylaxis and regular screening for viral associated malignancies of their child.

    

    

    Figure 2: Flow cytometric analysis of CD3, CD16 and CD56. Left panel
shows gated population and right dotplot shows complete absence of CD16
and CD56 whereas CD3 having normal expression.