Transfusion and Apheresis Science 50 (2014) 225–227
Contents lists available at ScienceDirect
Transfusion and Apheresis Science journal homepage: www.elsevier.com/locate/transci
Case Report
A rare case report of chronic variable immunodeficiency divulged by ABO discrepancy Atul Sonker a, Anju Dubey b,⇑, Ashutosh Singh a, Rajendra Chaudhary a a b
Department of Transfusion Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India Department of Transfusion Medicine, All India Institute of Medical Sciences, Rishikesh, India
a r t i c l e
i n f o
Article history: Received 20 August 2013 Accepted 1 November 2013
Keywords: ABO discrepancy Immunodeficiency Anti-A Anti-B
a b s t r a c t ABO discrepancy refers to incongruence between the results of red cell and serum groupings. One such case is described here; the discrepant results of whose routine ABO grouping led to the diagnosis of common variable immunodeficiency. There was no reaction in the reverse grouping of a young patient presenting with recurrent bacterial infections, pointing towards an absence of antibodies in the serum. Diagnosis was made on the basis of markedly decreased serum immunoglobulin levels and by serum protein electrophoresis showing scanty gamma regions. Ó 2014 Elsevier Ltd. All rights reserved.
1. Introduction ABO discrepancies are recognized when the reactions obtained in the forward (cell) grouping, are not in agreement with the reactions obtained in the reverse (serum) grouping. When a discrepancy is observed one must determine if the problem is associated with the forward grouping, reverse grouping or both. False negative reactions in the reverse grouping (class I ABO discrepancy) may be due to weak or missing antibodies, resulting from a variety of factors which influence the production of antibodies. Some of these are extremes of age, malignancies (leukemias and lymphomas), antibody dilution due to replacement fluids, immunosuppressive drugs, congenital agammaglobulinemia and other immunodeficiency conditions [1]. The titre of isohemagglutinins has also been reported to differ among ages, ethnic populations, and environment [2]. Common variable immunodeficiency is a rare but most clinically significant primary immune deficiency disease. ⇑ Corresponding author. E-mail addresses: [email protected] (A. Sonker), dranjudubey @gmail.com (A. Dubey), [email protected] (A. Singh), [email protected] (R. Chaudhary). http://dx.doi.org/10.1016/j.transci.2013.11.010 1473-0502/Ó 2014 Elsevier Ltd. All rights reserved.
It is characterized by low levels of serum immunoglobulin G, A, and/or M with loss of antibody production, lack of B lymphocytes or plasma cells that are capable of producing antibodies and frequent bacterial infections [3]. The diagnosis is often delayed, most commonly being made in adults between the ages of 20 and 40 yrs [3]. Diagnosis of CVID is usually made by demonstrating low levels of immunoglobulins in the serum, supplemented by exclusion of loss of protein from the kidneys, reduced antibody production secondary to chronic lymphocytic leukemia or multiple myeloma and other genetic causes of hypoglobulinemia [4,5]. Examining blood for pertinent isohemagglutinins is another common means of testing IgM anti-carbohydrate antibody production in older children and adults [6]. We have encountered this rare condition at our institute in a young adult patient; the discrepant results of whose routine ABO grouping led to the diagnosis of CVID.
2. Case report The patient was a 21 yr old college student who had been asymptomatic for the first 13 yrs of life, after which he was suffering from recurrent episodes of upper respiratory tract infections, intermittent fever, pain in abdomen,
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diarrhea and polyarthralgia. The patient was referred to our institute with a chief complaint of 4 days old right side hemi-paresis. His blood sample was sent to the immunohematology laboratory for routine ABO blood grouping. On a routine blood grouping test with a conventional test tube method, forward (cell) grouping showed no reaction with anti-A, anti-B (Eryclone, Tulip Diagnostics, Goa, India) and 4+ reaction with anti-D (Rhofinal, Tulip Diagnostics, Goa, India), thus suggesting the blood group to be O Rh D positive; however in reverse (serum) grouping, there was no reaction with A1 cells, B cells or O cells. To resolve this discrepancy, ABO grouping was repeated with conventional test tube method using a new lot of antisera, thrice washed patient cells and freshly prepared pooled cells (A1, B and O). Serum was added in double the amount than earlier for reverse grouping, but there was no reaction. The grouping tubes were further incubated at 4 °C and 18 °C for 30 min along with an autocontrol (to rule out interference with natural anti-I at this temperature). Still the tubes showed no reaction. To rule out weak subgroups of A or B, the technique of adsorption followed by elution was used. The adsorption was done using human anti-A and anti-B as some monoclonal ABO typing reagents are sensitive to changes in pH and osmolarity, therefore may not be suitable for adsorption and elution [7]. Heat elution was used to dissociate antibodies from the red cells. The eluate was tested against two examples of cells expressing the relevant antigen (A1 cells for suspected anti-A, B cells for anti-B). It was found to be non reactive at room temperature as well as 37 °C, thus suggesting that that the test cells do not express A or B antigen and cannot adsorb the relevant antibody. To confirm the secretor status, saliva grouping was performed which showed that the patient was a secretor of H substance. Thus, it provided an indication that patient’s blood group was O with absence of anti-A and anti-B antibodies in the serum. The patient’s records were reviewed and he was found to have no history of transfusion in the past. The clinical history of the patient pointed towards immunodeficiency and hence all relevant investigations were ordered. Laboratory results showed that the patient’s serum immunoglobulin levels were markedly decreased (Table 1) showing scanty gamma regions in serum protein electrophoresis and there was no Bruton’s tyrosine kinase
Table 1 Laboratory profile of the patient. Parameter
Levels
IgG IgA IgM Total serum protein Serum albumin Hb Hct WBC count Platelet count C reactive protein Serum AST (SGOT) Serum ALT (SGPT)
Contents lists available at ScienceDirect
Transfusion and Apheresis Science journal homepage: www.elsevier.com/locate/transci
Case Report
A rare case report of chronic variable immunodeficiency divulged by ABO discrepancy Atul Sonker a, Anju Dubey b,⇑, Ashutosh Singh a, Rajendra Chaudhary a a b
Department of Transfusion Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India Department of Transfusion Medicine, All India Institute of Medical Sciences, Rishikesh, India
a r t i c l e
i n f o
Article history: Received 20 August 2013 Accepted 1 November 2013
Keywords: ABO discrepancy Immunodeficiency Anti-A Anti-B
a b s t r a c t ABO discrepancy refers to incongruence between the results of red cell and serum groupings. One such case is described here; the discrepant results of whose routine ABO grouping led to the diagnosis of common variable immunodeficiency. There was no reaction in the reverse grouping of a young patient presenting with recurrent bacterial infections, pointing towards an absence of antibodies in the serum. Diagnosis was made on the basis of markedly decreased serum immunoglobulin levels and by serum protein electrophoresis showing scanty gamma regions. Ó 2014 Elsevier Ltd. All rights reserved.
1. Introduction ABO discrepancies are recognized when the reactions obtained in the forward (cell) grouping, are not in agreement with the reactions obtained in the reverse (serum) grouping. When a discrepancy is observed one must determine if the problem is associated with the forward grouping, reverse grouping or both. False negative reactions in the reverse grouping (class I ABO discrepancy) may be due to weak or missing antibodies, resulting from a variety of factors which influence the production of antibodies. Some of these are extremes of age, malignancies (leukemias and lymphomas), antibody dilution due to replacement fluids, immunosuppressive drugs, congenital agammaglobulinemia and other immunodeficiency conditions [1]. The titre of isohemagglutinins has also been reported to differ among ages, ethnic populations, and environment [2]. Common variable immunodeficiency is a rare but most clinically significant primary immune deficiency disease. ⇑ Corresponding author. E-mail addresses: [email protected] (A. Sonker), dranjudubey @gmail.com (A. Dubey), [email protected] (A. Singh), [email protected] (R. Chaudhary). http://dx.doi.org/10.1016/j.transci.2013.11.010 1473-0502/Ó 2014 Elsevier Ltd. All rights reserved.
It is characterized by low levels of serum immunoglobulin G, A, and/or M with loss of antibody production, lack of B lymphocytes or plasma cells that are capable of producing antibodies and frequent bacterial infections [3]. The diagnosis is often delayed, most commonly being made in adults between the ages of 20 and 40 yrs [3]. Diagnosis of CVID is usually made by demonstrating low levels of immunoglobulins in the serum, supplemented by exclusion of loss of protein from the kidneys, reduced antibody production secondary to chronic lymphocytic leukemia or multiple myeloma and other genetic causes of hypoglobulinemia [4,5]. Examining blood for pertinent isohemagglutinins is another common means of testing IgM anti-carbohydrate antibody production in older children and adults [6]. We have encountered this rare condition at our institute in a young adult patient; the discrepant results of whose routine ABO grouping led to the diagnosis of CVID.
2. Case report The patient was a 21 yr old college student who had been asymptomatic for the first 13 yrs of life, after which he was suffering from recurrent episodes of upper respiratory tract infections, intermittent fever, pain in abdomen,
226
A. Sonker et al. / Transfusion and Apheresis Science 50 (2014) 225–227
diarrhea and polyarthralgia. The patient was referred to our institute with a chief complaint of 4 days old right side hemi-paresis. His blood sample was sent to the immunohematology laboratory for routine ABO blood grouping. On a routine blood grouping test with a conventional test tube method, forward (cell) grouping showed no reaction with anti-A, anti-B (Eryclone, Tulip Diagnostics, Goa, India) and 4+ reaction with anti-D (Rhofinal, Tulip Diagnostics, Goa, India), thus suggesting the blood group to be O Rh D positive; however in reverse (serum) grouping, there was no reaction with A1 cells, B cells or O cells. To resolve this discrepancy, ABO grouping was repeated with conventional test tube method using a new lot of antisera, thrice washed patient cells and freshly prepared pooled cells (A1, B and O). Serum was added in double the amount than earlier for reverse grouping, but there was no reaction. The grouping tubes were further incubated at 4 °C and 18 °C for 30 min along with an autocontrol (to rule out interference with natural anti-I at this temperature). Still the tubes showed no reaction. To rule out weak subgroups of A or B, the technique of adsorption followed by elution was used. The adsorption was done using human anti-A and anti-B as some monoclonal ABO typing reagents are sensitive to changes in pH and osmolarity, therefore may not be suitable for adsorption and elution [7]. Heat elution was used to dissociate antibodies from the red cells. The eluate was tested against two examples of cells expressing the relevant antigen (A1 cells for suspected anti-A, B cells for anti-B). It was found to be non reactive at room temperature as well as 37 °C, thus suggesting that that the test cells do not express A or B antigen and cannot adsorb the relevant antibody. To confirm the secretor status, saliva grouping was performed which showed that the patient was a secretor of H substance. Thus, it provided an indication that patient’s blood group was O with absence of anti-A and anti-B antibodies in the serum. The patient’s records were reviewed and he was found to have no history of transfusion in the past. The clinical history of the patient pointed towards immunodeficiency and hence all relevant investigations were ordered. Laboratory results showed that the patient’s serum immunoglobulin levels were markedly decreased (Table 1) showing scanty gamma regions in serum protein electrophoresis and there was no Bruton’s tyrosine kinase
Table 1 Laboratory profile of the patient. Parameter
Levels
IgG IgA IgM Total serum protein Serum albumin Hb Hct WBC count Platelet count C reactive protein Serum AST (SGOT) Serum ALT (SGPT)
