A low neutrophil count along with a high lymphocyte count can be an indication of viral infections, autoimmune diseases and leukemias. The current article provides information regarding the absolute counts of these cell types, as well as the diseases that lead to high lymphocytes and low neutrophils.
Neutrophils and lymphocytes are types of white blood cells that play an important and unique role in providing immunity against infections. Abnormal numbers of these cells influence the body’s ability to fight infections. Abnormally low neutrophil count (neutropenia) as well as a high lymphocyte count (lymphocytosis) can be the result of viral infection or an indication of the adult-onset form of cyclic neutropenia, certain lymphoproliferative disorders like lymphomas and leukemias or certain autoimmune diseases.
Neutrophils belong to the class polymorphonuclear granulocytes, and have a multilobed nucleus. These phagocytic cells provide the first line of defense against foreign bodies and pathogens, and play a major role in activating an immune response against a pathogenic agent. They occupy the highest count amongst white blood cells, and are divided into two types, segmented neutrophils (segs or polys) and banded neutrophils (bands). Segmented neutrophils circulate in a mature form, and possess a divided or segmented nucleus; while banded neutrophils are immature, and have a band-shaped nucleus. Decreased neutrophils, can be the result of immunosuppressive drugs, antipsychotics, chemotherapy, as also certain viral diseases. Neutropenia results in compromised immunity, and increases the susceptibility to infections.
Lymphocytes form the primary component of the processes that confer adaptive immunity. These are categorized as B lymphocytes, T lymphocytes and natural killer (NK) cells or large granular lymphocytes (LGL). The B lymphocytes participate in immune response by antibody production, whereas the T lymphocytes bring about the destruction of pathogens or infected cells with the help of such antibodies. NK cells are cytotoxic lymphocytes that bring about the destruction of infected cells in an antibody-dependent as well as antibody-independent processes. Increase in lymphocytes is generally the result of acute bacterial and viral infections, leukemias, lymphomas, ulcerative colitis, and acute-phase reactions (observed as a response to acute stress).
Certain diseases and disorders exhibit a combination of both neutropenia and lymphocytosis. Before understanding these causes, it is essential to know the difference between absolute and relative cell counts used to indicate the amount of a cell type. Given below is some information about the same, as well as the causes leading to a condition of low neutrophils coupled with high lymphocytes.
Absolute and Relative Counts
Absolute count refers to the actual concentration of cells, whereas a relative count refers to the amount of cells expressed as a percentage of the total number of white blood cells. The normal and abnormal ranges for absolute neutrophil counts (ANC) and absolute lymphocyte concentrations in adults are as follows:
Absolute Neutrophil Count (ANC)
(cells per µl of blood)
- Normal range: 1500-8000
- Mild neutropenia: 1000-1500
- Moderate neutropenia: 500-1000
- Severe neutropenia: below 500
Absolute Lymphocyte Count (ALC)
(cells per µl of blood)
- Normal range: 1000 to 4000
- Lymphocytosis: above 4000
To correctly identify the physiological presence of both neutropenia and lymphocytosis, the absolute counts as well as the relative counts of the two cell types need to be considered. Relative count alone does not accurately indicate the physiological status. For example, in case of an individual with neutropenia but normal lymphocyte amounts, the relative count analysis will show a lower percentage of neutrophils, but at the same time reflect a high percentage of lymphocytes. This is simply the outcome of measurement in percentages, and not because of a physiological increase in the number of lymphocytes.
Mild neutropenia and lymphocytosis are a common manifestation of several viral infections including mumps, measles, influenza, hepatitis and infectious mononucleosis. The elevated count of lymphocytes is a result of the body’s attempt to fight the infection. Also, an increase in lymphocytes may occur due to abnormalities introduced by the virus or viral derivatives. High numbers of such atypical lymphocytes contributes to the decrease in neutrophils by affecting the processes of neutrophil production and maturation.
Adult-onset Cyclic Neutropenia
Cyclic neutropenia is a genetic disorder that is characterized by a periodic decrease in neutrophil count. During the neutropenic phase, which lasts for 3-5 days, the number of neutrophils (ANC) drops below 200 cells per µl of blood. After this phase, the counts increase, and remain at 200 cells per µl of blood for about 21 days. Such a decrease occurs due to a genetic mutation that reduces the life-span of neutrophils. The adult-onset form of this disease is characterized by lymphocytosis due to an increase in the number of large granular lymphocytes (LGL).
The patient often experiences repetitive episodes of malaise, fever, infections and ulcers. Treatment includes the administration of G-CSF (granulocyte colony stimulating factor) which is a growth factor that promotes the survival, proliferation and differentiation of neutrophils. Symptomatic treatments include the use of steroids and antibiotics like cephalosporin.
Lymphomas are characterized by the formation of solid tumors due to an abnormal increase in mature lymphocytes. They are broadly categorized as Hodgkin’s and non-Hodgkin lymphomas, depending on the precise pathology. When such tumorigenic cells infiltrate the bone marrow, the proliferation and differentiation of neutrophils is affected leading to neutropenia, revealed by a low ANC.
The common symptoms include swollen lymph nodes, fever, night sweats, fatigue, itchy skin, as well as abdominal pain and discomfort due to splenomegaly and/or hepatomegaly. A combination of chemotherapy and radiation therapy is the general approach to deal with the tumors. The precise drugs, dosage and their combination depends on the type of lymphoma, its stage, and the age, sex and medical history of the patient.
The different types of leukemias that are associated with neutropenia are:
- Large granular lymphocyte (LGL) leukemia
- T-cell large granular lymphocyte (T-LGL) leukemia
- Acute myeloid leukemia (AML)
- Acute lymphocytic leukemia (ALL)
- Chronic lymphocytic leukemia (CLL)
LGL and T-LGL leukemias arise due to an uncontrolled proliferation of NK cells and cytotoxic T-cells respectively, and are the most common leukemias that cause neutropenia. AML, ALL and CLL involve the clonal expansion of progenitor lymphocytes. As a result, the lymphocyte counts in such patients are high. Such uncontrolled clonal expansion interferes with the normal production and differentiation of neutrophils as well. For some patients, the lab test may indicate a normal WBC count, and hence a differential count and bone marrow test is essential for the right diagnosis.
Night sweats, frequent colds, fatigue, recurring infections, loss of appetite and weight loss are the associated symptoms. Symptomatic treatments along with chemotherapy involving drugs like daunorubicin, fludarabine, rituximab, alemtuzumab, etc. is the general option for reducing the lymphocyte count. Choice of the drug varies with each individual patient. Radiation therapy and bone marrow transplant may be advised for certain cases involving the development of secondary cancers.
Certain autoimmune diseases including Felty syndrome (occurs in association with rheumatoid arthritis) and systemic lupus erythematosus (SLE) are characterized by an inflammatory response, and involve an increase in the number of LGLs. These cells infiltrate the bone marrow and hamper neutrophil production. Hence, a combined state of neutropenia and lymphocytosis may be observed.
Felty syndrome involves joint pain and swelling, recurrent infections, fatigue, bone and joint deformities, etc. SLE is characterized by the development of a butterfly rash on the face along with hair loss, mouth sores, fever and increased sensitivity to sunlight. The treatments are often symptomatic, and include the use of analgesics, and anti-inflammatory drugs. Immunosuppressive drugs are also used to reduce the activity of immune system.
The quality and quantity of neutrophils and lymphocytes is crucial for the efficient functioning of the immune system. In addition, the balance between neutrophils and lymphocytes, indicated by neutrophil to lymphocyte ratio (NLR), is being studied extensively. The aim is to develop a standard diagnostic parameter for systemic inflammation, which is essential to provide a prognosis for patients suffering with cardiovascular diseases, cancers, as well as patients critically ill due to surgeries, multiple trauma, shock, etc. However, it is imperative to consult a hematologist or an appropriate expert, and undergo further investigation to confirm the diagnosis and etiology.
Disclaimer: This HealthHearty article is for informative purposes only, and should not be used as a substitute for professional medical advice.