[PAGID] Hypogamma with monoclonal IgM, Lymphopenia, no B-cells, high ratio of CD4+/CD8+ cells

[Maria Kanariou]

I would appreciate suggestions on the diagnosis and management of a case
regarding a 6 month-old boy, with Interstitial Pneumonitis (following viral
gastroenteritis), low IgG, high IgM levels (monoclonal IgM) and Lymphopenia
with almost no B-cells, high percentage of T-cells with extremely high ratio
of CD4+/CD8+ cells.  It has to be noticed that only immunoglobins have been
performed at his admission.

                        

At the age of 5,5 months he was admitted at the Pediatric Dept, because of
an episode of febrile diarrhea, vomiting and decreased feeding and loss of
weight. He received  "fluids" and metronidazol. Dyspnea, tachypnea,
desaturation and grunting were added and he was transferred to the PICU. His
sister and parents had similar episode without any complication.

 

The chest radiograph showed diffuse confluent opacities mainly in lower
lobes and methylprednisolone (2mg/kg) was given and chest CT showed
consolidations-atelectasies mainly in lower lobes with many interstitial
elements and hyperinflation in upper parts, and lymph nodes smaller than 8mm
in axillae bilaterally. 

 

On a PBC before admission, he had Lymphopenia (15%, 1.880/μl). During
hospitalization his Lymphopenia was more prominent with Lymphocyte counts
ranging around 600/μl. (Noticeable that he had received corticosteroids).

 

IgG levels were constantly low, IgA levels were normal for his age and IgM
levels were initially remarkably elevated (205 mg/dl) with small zone of
monoclonality (IgM-κ). It has decreased to normal after gamma-globulin.

 

Antibody response to Te, Hib and Pn (after 2 doses of the respective
vaccines for his age) was lower than normal. 

 

Hb, PLT, Liver and kidney function as well as the other routine tested
parameters were within normal range.  

 

Immunological findings  a week later while he was in PICU and had already
received corticosteroids, pentaglobin & IVIG.

 

WBC: 8600/μl, Lymphocytes: 600/μl (7.2%)

Lymphocyte immunophenotype in peripheral blood revealed increased percentage
but low absolute number of CD3 (89%, 553/μl). Most of the T-cells were CD4+,
with only 5%, CD3+CD8+ cells (33/μl) and there was a higher than normal for
his ages proportion of memory CD4+ cells. B-cells were undetectable. 

 

CD40L expression on stimulated CD4+ (CD8-) lymphocytes was proportionate to
that of normal control.

 

TCR - Vβ repertoire of CD4+ T cells was not skewed 

 

Investigation for himaera showed no maternal lymphocytes. 

 

Lymphocyte immunophenotype in Bone marrow aspiration specimen: 

B-cell precursors were undetectable. A minimal proportion of mature B-cells
(CD19+CD10-CD20+) was detected (33 B-cells /100,000 nucleated cells) and
this finding was interpreted with caution since it is slightly over the
detection limit of the method. (Noticeable that there was excessive
contamination of peripheral blood).

 

There is no HLA matched sibling. 

 

Microbiological investigation: 

Clostridium difficile was isolated in fecal culture. PCR in blood and BAL
revealed no microorganism (EBV, CMV, Adenovirus, Influenza virus,
Enteroviruses, Parvovirus). Mycoplasma and Chlamydia were not detected in
BAL fluid. RSV, Rotavirus, HIV negative. Nasal Ag for influenza, Ag in urine
for Legionella, BAL for P. carinnii: negative. Screening for Candida and
Aspergillus in BAL and Blood: negative). 

 

Management: 

He is under antibiotics (including septrin), antifungal and antiviral drugs.


Pentaglobin was administered on his admission at the PICU and since then he
is under IVIG replacement, and steroids are given systematically. 

The infant remains (about a month) under mechanical ventilation needing FiO2
around 50%, because of deterioration of lung function. 

 

 

Maria Kanariou

 

Maria G. Kanariou, MD

Consultant in Paediatric Immunology

Center for Primary Immunodeficienies-Paediatric Immunology

"Aghia Sophia" Children's Hospital

Thivon & Papadiamantopoulou str., Goudi

11527 - Athens - Greece

Tel.: +30-2107467766

Fax: +30-2107757401

  

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