Mannose Binding Lectin Deficiency

Mannose binding lectin deficiency is the commonest inherited immune deficiency, caused by variants in MBL2. Most affected people are healthy, and it matters mainly when other immune defects are present.

Pathophysiology. Mannose binding lectin recognises sugar patterns on microbes and starts lectin activation of complement through MASP-2, which promotes opsonisation and clearance. Three coding variants in exon 1 (B, C and D) and promoter variants lower the serum level.

Low levels are found in roughly 5 to 10% of people, and a larger group has reduced levels, with frequencies varying across populations.

The link to disease is weak. Any raised risk is greatest in infants aged 6 to 24 months, patients with neutropenia or immunosuppression, and people with cystic fibrosis or bronchiectasis.

• Most people have no symptoms
• Recurrent upper and lower respiratory tract infection in infancy
• Severe infection during chemotherapy induced neutropenia or after transplantation
• More severe lung disease in cystic fibrosis
• Recurrent vulvovaginal candidiasis in a few
• Possible associations with autoimmune disease and atherosclerosis, which are weak and not proven to be causal

• Serum MBL level by immunoassay (low if under about 100 nanogram/mL, with laboratory specific limits), supported by functional assays of lectin activation.
• MBL2 genotyping (exon 1 and promoter variants) for confirmation.
• Total haemolytic complement (CH50): normal, since lectin activation is separate from classical activation.
• Exclusion of other causes of infection: immunoglobulins, specific antibody responses, lymphocyte subsets, complement screen, HIV test and, in children, a sweat test.
• Do not test routinely in people with infection alone; a low result seldom changes management when other defects are absent.

Differential diagnosis.

• Antibody deficiency (common variable immunodeficiency, specific antibody deficiency)
• Other complement deficiencies and MASP-2 deficiency
• Neutrophil disorders and chronic granulomatous disease
• Cystic fibrosis and primary ciliary dyskinesia
• HIV infection
• Allergic and structural causes of recurrent respiratory infection

• Asymptomatic people with a low level: no treatment is needed; explain that the finding is common and benign.
• Recurrent infection: exclude other immune defects first, treat infections early by culture, and give routine vaccination, with yearly inactivated influenza vaccine and pneumococcal conjugate vaccine.
• Antibiotic prophylaxis is considered only when infections are frequent and other causes are excluded: azithromycin 500 mg orally three times weekly or 250 mg daily in adults (children 10 mg/kg three times weekly, maximum 500 mg), after ECG shows QTc under 450 ms and sputum is clear of non-tuberculous mycobacteria.
• Neutropenia or transplantation: manage neutropenic fever in the usual way with piperacillin with tazobactam 4.5 g intravenously every 6 hours in adults, and do not give MBL replacement.
• MBL replacement with plasma derived or recombinant protein is experimental and is not used outside research.
• Cystic fibrosis and bronchiectasis: usual airway clearance and antibiotic care apply, unchanged by MBL status.
• Vulvovaginal candidiasis: fluconazole 150 mg orally on days 1, 4 and 7, then 150 mg weekly for 6 months for recurrence (reduce at creatinine clearance under 50 mL/min).

Special groups.

• Infants aged 6 to 24 months with recurrent infection: reassess for other immunodeficiency before attributing the problem to low MBL.
• Chemotherapy patients: low MBL may add to infection risk, but it does not change the supportive care already given.

Monitoring. No routine monitoring if healthy. Clinical review for patients with recurrent infection every 6 to 12 months, with a repeat immune evaluation if the pattern changes.

Referral and escalation. Refer to immunology when infections are severe, opportunistic or recurrent despite a normal MBL result, or when other defects are suspected. Urgent for sepsis in a neutropenic patient.